Assessing The Development And Risk Factors Of Keratoconus Biology Essay

The eyes are the primary ocular organ of an being.

Being portion of the specific sensory system for vision, the oculus converts ocular visible radiation into a form of ranked action potencies which can so be interpreted by the encephalon as an image ( Widmaier et al. , 2008 ) .The oculus is a complex organ with extremely differentiated tissues, each holding specific maps in order to accomplish vision. The outer part of the oculus is made up of three beds ; the sclerotic coat which forms a tough, protective capsule, the choroid which is a in darkness pigmented bed to absorb beams of visible radiations at the dorsum of the oculus and the retina which is made up of specific photo-sensitive receptor cells to observe the light beams come ining the oculus. Within these beds are two fluid-filled Chamberss separated by the lens of the oculus. To let the entry of beams of visible radiations into the oculus, the anterior surface of the sclerotic coat specialised into the cornea while the choroid forms the flag ( the coloured-structure of the oculus ) , the ciliary musculus ( which controls the form of the lens for concentrating ) and the zonular fibres ( which holds the lens in topographic point ) . The anatomy of a human oculus can be seen in Figure 1.

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1.Vision is acquired by concentrating beams of light onto a individual point on the retina, the fovea centralis through the refractile actions of some constructions in the oculus. In order to accomplish a clear vision, visible radiation from the environment enters the oculus through the cornea, and is focused by the lens onto the fovea centralis.

As this part of the retina has the highest ocular sharp-sightedness, failure of the oculus to concentrate light onto fovea centralis consequences in bleary images and such conditions are known as refractile mistakes ( Benjamin, 2006 ) .

Refractive Mistakes

Harmonizing to the World Health Organisation ( WHO ) , refractile mistakes are really common oculus upsets in which the oculus can non clearly focus images from the surrounding, ensuing in blurred vision and in terrible instances, ocular damage. It was estimated that about 153 million people world-wide suffers from ocular damages due to uncorrected refractile mistakes ( World Health Organization, 2009 ) . Two of the most common signifier of refractile mistakes present in healthy persons are myopia and astigmia.


Myopia, or normally known as near-sightedness, is a status in which the beams of light come ining are focused in forepart of the retina. Such a status may happen due to the oculus holding an extended axial length ( which is the consecutive length from the cornea to the fovea centralis ) or an addition in refractile ( concentrating ) power in one or more refractile constituents of the oculus, such as the cornea or the lens ( Borish, 1970 ) .Due to the legion signifiers of nearsightedness reported, many categorization methods have been suggested.

However, a reappraisal of the methods of categorization by Grosvenor ( 1987 ) proposed seven wide headers for sorting nearsightedness, which were rate of nearsightedness patterned advance, anatomical characteristics of nearsightedness, grade of nearsightedness, physiological and pathological nearsightedness, familial and environmentally induced nearsightedness, theory of nearsightedness development and age of nearsightedness oncoming. For this survey, the grade of nearsightedness was used whereby topics were grouped based on disciplinary power required which were high ( more than -6.00 D ) , moderate ( between -3.

00 to -6.00 D ) , low ( between -0.25 to -3.00 D ) and normal ( between -0.25 to 0.00 ) ( Cline et al. , 1997 ) .


Astigmatism, on the other manus, is the failure of the cornea to concentrate visible radiation on a individual point on the retina due to the difference in refractile powers of different radial planes of the cornea.

This therefore consequences in two centres of focal point which cause deformation of the image seen ( Shapiro, 1984 ) . If the angle between the plane with the highest refractile power and that with the lowest is perpendicular are one another, the astigmia is considered regular. Otherwise, it would be considered an irregular astigmia ( Duke-Elders et al. , 1970 ) . Irregular astigmia should be noted as it is a mark of possible corneal deformation and cutting ( Szczotka-Flynn et al. , 2006 ; Rabinotwiz, 1998 ) .

The Cornea

Harmonizing to the National Eye Institute, the cornea is the clear, dome-shaped, outermost bed that covers the forepart of the oculus. It is made up of five beds ; the outermost epithelial tissue, the Bowman ‘s bed, the stroma, the Descemet ‘s membrane and the endothelium.

Functions of the cornea include screening the interiors of the oculus from harmful elements from the environment and controlling and concentrating the beams of light come ining the oculus. Hence, any hurt to the cornea may ensue in terrible ocular loss. As the cornea is invariably exposed to the injuries of the environment, the cornea must be able to get by and react fleetly to amendss or any hurts caused by the environment before vision is affected.

Failure of the cornea to make so may take to the development of corneal diseases and upsets. ( National Eye Institute, 2010 ) .


Keratoconus ( KC ) is most common primary ectasis of the cornea, characterised by bilateral, asymmetric, localised cutting of the corneal which leads to bulge and coning of the cornea ( Krachmer et al. , 1984 ) . As the corneal cutting progresses, one begins to develop high refractile mistakes and irregular astigmia which badly affect ocular sharp-sightedness ( Jimenez et al. , 2010 ) . KC has been indicated to hold an oncoming at pubescence, which normally progresses until the 4th decennary of life ( Rabinowitz, 1998 ) . However, instances of KC developing earlier ( Rahmen et al.

, 2006 ) or later in life ( Lim et al. , 2003 ) and even at birth, though seldom ( Smolin, 1987 ) have been reported.

Clinical Features of KC

At a cellular degree, KC has frequently been characterised by three classical histopathological marks ; thinning of the corneal stroma, breakage in the Bowman ‘s bed, and Fe deposition within the basal bed of the corneal epithelial tissue ( Rabinowitz, 1998 ) . However, a more recent study in the histopathology of KC indicated other alterations such as thickener of nervus fibers, irregular and broken cellar membrane and apoptotic cells in the epithelial tissue ( Sherwin et al. , 2004 ) .As cellular pathogenesis advancements, typical marks and symptoms starts to look depending on the badness of KC nowadays.

At subclinical phases, KC is present as forme fruste KC which does non bring forth any noticeable symptoms. Therefore, forme fruste KC frequently remains undetectable by both patients and testers unless specific optic scrutinies have been carried out ( Arntz et al. , 2003 ) .As the disease progresses, patients begins to endure from important vision sharp-sightedness impairment which can non be corrected with eyeglassess and increasing irregular astigmia ( Krachmer et al. , 1984 ) . Once KC has reach moderate to terrible degrees, obvious physical marks can be detected. Slit lamp findings normally presented in KC patients are stromal cutting, Vogt ‘s striae ( which are all right lines parallel to the axis of the cone found in the deep stroma and Descemet ‘s membrane ) , Fleischer ‘s ring ( accretion of Fe sedimentations environing the cone ) and corneal scarring on the epithelial or subepithelial bed ( McMahon, 2006 ) , as shown in Figure 1.

1.However, the most of import tool for naming KC in recent times would hold to be corneal topography. Promotions in naming KC with corneal topography have proved to be valuable in documenting the different forms of the anterior corneal surface in KC patients, which may supply new information of the possible pathogenesis tract of this upset ( Rabinowitz at al. , 1989 ) . In fact, the usage of corneal topography is of import particularly in the sensing and certification of corneal abnormalities in the early phases of KC, such as in forme fruste KC as it was reported that big sums of corneal distortion were detected in the cornea of several KC suspects despite showing normal keratometry and refractile informations, in add-on to normal slit lamp findings ( Maguire et al. , 1989 ) .

Through corneal topography, both KC and forme fruste KC can be detected by an “ asymmetric bow tie with skewed radial axis ” form ( Figure 1.2 ) seen in the corneal topograph ( Rabinowitz, 2007 ) .In recent old ages, enormous attempt have besides been made to ease sensing of KC utilizing corneal topography, particularly during the forme fruste phase through the development of several index-based categorization methods as reported by Maeda & A ; Klyce ( 1994 ) , Smolek & A ; Klyce ( 1997 ) , Schwiegerling & A ; Grevenkamp ( 1996 ) , Rabinowitz & A ; Rasheed ( 1999 ) , McMahon et Al. ( 2006 ) and Mahmoud et al. ( 2008 ) . To day of the month, there are two optical instruments with built-in package based on these indices which can observe and supervise the patterned advance of KC ; the Pentacam ( Emre et al.

, 2007 ) and the Ocular Response Analyzer ( Fontes et al. , 2010 ) . As more accurate indices are being developed as clip base on ballss, research workers comes closer and closer to deducing the perfect expression to observing the earliest phases of KC which can turn to the subjective nature of naming KC.Despite the heavy dependance of current KC diagnostic methods on computer-assisted optical measurement instruments, the strong familial nexus found in KC have opened a new door for research workers to develop new diagnostic methods based on molecular familial trials. However, most are still in development phase and far from ready for clinical usage ( Rabinowitz, 2007 ) .


In literature, the most common prevalence of KC was approximative to be approximately 1 in 2000 in the general population ( Krachmer et al. , 1984 ) . However, this value may change well between different populations with studies of every bit low as 4 per 100,000 ( Duke-Elders & A ; Leigh, 1965 ) to every bit high as 600 per 100,000 ( Hofstetter, 1959 ) .

However, it was found that most studies of KC prevalence were based on western populations and studies on prevalence of KC in Asiatic population remain scarce ( Mahadevan et al. 2009 ) . Several surveies have indicated higher incidences of KC among Asian-Indians arising from Northern Pakistan when compared to Caucasians from the same country ( Pearson et al. , 2000 ; Georgiou et al. , 2004 ) . There have besides been studies of increased KC look among the Mediterranean and Middle Eastern populations, which could hold been influenced by the hot, dry clime nowadays at that place ( Tanabe et al. , 1985 ; Tabbara, 1999 ; De Cock, 1994 ) while populations made up of high per centums of Chinese showed lower prevalence ( Shi et al. , 2007 ) .

In Malaysia, literature on KC were limited or none being. In a survey on the causes of childhood sightlessness in Malaysia carried out pupils from six schools for the blind found that out of the 332 kids identified, merely eight ( 2.4 % ) suffered from KC ( Reddy & A ; Tan, 2001 ) while in the territory of Gombak, merely a mere 0.3 % of school-aged kids there were diagnosed with KC ( Goh et al. , 2005 ) . A survey similar survey carried out under an urban scene found that 0.3 % of oculus patients of the UMMC were KC ( Reddy et al.

, 2008 ) . However, these studies do non stand for the existent figure reasonably and the prevalence in Malaysia may be much higher than those reported.

Hazard Factors

Despite heavy attempts put into research of the possible aetiology and pathogenesis of KC over the last few decennaries, consequences have remained inconclusive and ill understood. There have been several indicants of an implicit in familial factor, and besides links to possible biochemical and biomechanical mechanisms ( Jimenez et al. , 2010 ) .

KC is a heterogeneous disease, with several indicants of familial factors lending to the pathogenesis of stray KC such as bilateralism of the disease, duplicate surveies, familial collection and formal familial analyses ( Rabinowitz, 2003 ) . Out of the 19 braces of monozygotic twins affected by KC have been reported in literature to day of the month, most reported of KC prevalence in both twins, but at different degrees of badness. This suggested the strong familial factor over the development of KC, but besides indicates the function of environmental factors ( Parker et al. , 1996 ; Weed et al.

, 2006 ; Bechara & A ; Waring, 1996 ) . Early familial surveies indicated familial dealingss were present in 6-8 % of KC topics ( Hammerstein, 1974 ) . However, the innovation of corneal topography had more or less confirmed the function of familial dealingss in KC development with findings of up to 50 % of KC topics holding at least one affected household member ( Gonzalez & A ; McDonnell, 1992 ) . This association was farther strengthen by recent findings that relations of KC patients had a hazard of up to 67 times higher to develop KC compared to those who did non ( Wang et al. , 2000 ) . Few familial analyses have identified possible mutants present in KC patients, nevertheless consequences remain inconclusive and conflicting ( Jimenez et al. , 2010 ) .Theories on a biochemical mechanism have been suggested by some research workers, most of which supports the hypothesis that loss of corneal structural constituents finally leads to KC development.

Although really small is known about the mechanisms taking to ectasia in KC, a current hypothesis is that the cutting of the cornea is due to abnormalcy in the collagen cross-linking and subsequent stromal thinning which leads to bulge of the cornea ( Li et al. , 2007 ) . Other research lab surveies have besides indicated increased degrees of peptidases and lessening degrees of peptidase inhibitors such as I±2-macroglobulin and I±1-antiprotease in the eyes of KC patients ( Fukuchi et al.

, 1994 ; Sawaguchi et al. , 1989 ; Sawaguchi et al. , 1994 ) . Another strong hypothesis for the development of KC pointed out the function of the interleukin-1 system and other programmed cell death modulating systems which contributes to loss of keratocytes and finally stromal cutting ( Wilson et al. , 1996 ) .From a biomechanical facet of the development of KC, most surveies have pointed towards the function of oxidative harm to corneal tissue in KC eyes. Both common hazard factors of KC, immediate allergy and mechanical injury cause by oculus rubbing have been implicated to do oxidative harm to the cornea ( Kenney & A ; Brown, 2003 ) .

The function of immediate allergy in the development of KC have been ill-defined as initial studies of association between KC and immediate allergy was most likely because atopic persons have a inclination for oculus rubbing due to the terrible scabies they suffer ( Bawazeer et al. , 2000 ) . However, there have been surveies which found topographic differences and faster KC development in atopic persons compared to normal persons ( Kaya et al. , 2007 ; Hargrave et al. , 2003 ) .

Hence, most probe is needed to corroborate such associations. Mechanical injury caused by oculus friction have besides been implicated legion times as a important hazard factor of KC due to the high per centum of KC patients with positive history of oculus friction, runing between 66 % ( Coperman, 1965 ) to 73 % ( Karseras & A ; Ruben, 1976 ) . However, a causal relationship is still difficult to corroborate as grounds for oculus rubbing being a hazard factor is circumstantial, based merely on clinical observation and subjective response ( Koenig & A ; Smith.

,1993 ) . McMonnies ( 2007 ) argued though, that it was still sensible to reason oculus rubbing as the cause of non all but some signifiers of KC, because oculus friction is non a necessary status for KC development despite its circumstantial nature.


Paraoxonase 1 ( PON1 ; EC 3.1.

1.2/ EC ) is a calcium-dependent esterase which is physically associated to high-density lipoprotein ( HDL ) molecules. PON1 was ab initio discovered for its ability to hydrolyze the organophosphate paraoxon, therefore the name given ( Durrington et al.

, 2001 ) . PON1 has two EC appellations as it was ab initio thought that PON1 and arylesterase were two different enzymes. However, subsequent research demonstrated that PON1 was besides responsible for the arylesterase activities ( Sorensen et al. , 1995 ) .

The PON Family

The PON1 cistron encoding for the enzyme, belongs to a ace household of PON cistrons. Together with PON2 and PON3, the PON cistron household is located on the long arm of human chromosome 7 at place q21.22 ( Primo-Parmo et al. , 1996 ) .

With grounds of high similarities between the PON cistrons at the amino acid and base degrees, there are strong indicants that these cistrons may hold a common evolutionary precursor, with PON2 being the oldest member followed by PON3 and PON1 ( Draganov & A ; La Du, 2004 ) . With the find of the protective effects of PON1 towards low-density lipoprotein ( LDL ) and HDL, there has been a enormous rise in the figure of surveies on PON1 ( Aviram, 2004 ) . PON2 and PON3, although less studied, have besides been shown to expose antioxidant belongingss and possible antiatherogenic capacities similar to PON1 ( Ng et al. , 2004 ) .

Biochemical Structure and Active Sites

PON1 is made up of 354 aminic acids with a entire molecular weight of 43 kDa ( Primo-Parma et al. , 1996 ; Mackness et al. , 1996 ) . PON1 courier ribonucleic acid ( messenger RNA ) look is limited to the liver in worlds.

When secreted into the blood circulation, PON1 entirely binds to HDL ( Mackness, 1989a, 1989b ) .At a molecular degree, the PON1 protein consists of six I?-bladed propellors, with four I?-strands doing up each blade at shown in Figure. At the top of the propellor, three I±-helices are responsible for the binding of PON1 to the HDL molecule. Calcium have besides been shown to be of import in PON1 activity, by keeping the active site of PON1 through direct engagement or keeping appropriate conformation of the active site, and by easing the remotion of diethyl phosphates from the active site ( Harel et al.

, 2004 ) . The Apolipoprotein-A1 ( apoA1 ) in HDL molecules have besides been implicated to stabilise and excite hydrolytic activities of PON1 ( Rosenblat et al. , 2006 ) .

Biochemical Function

As PON1 has two active sites specific to different substrates, the biochemical maps of PON1 can be classified harmonizing to which active sites present contributed to the biochemical map. The calcium-dependent site of PON1 has been attributed to ability to hydrolyze organophosphates and related substrate, therefore perchance supplying protection against organophosphate neurotoxicity ( Costa et al. , 2005a ) . On the other manus, a Cys283 residue-dependent site contributes to PON1 ability to hydrolyze oxidized lipoids. Therefore, it has been set up for some clip already of the function of PON1 in the development of coronary artery disease ( Mackness & A ; Mackness, 2004 ) , chiefly due to its protective effects towards LDL against oxidization and by stimulation of the HDL-mediated macrophage cholesterin outflow ( Rosenblat et al. , 2006 ) .In vitro, PON1 have been successfully shown to hydrolyze active metabolites of organophosphates such as paraoxon, chlorpyrifos oxon and diazoxon, and besides nerve agents such as GD and GB ( Costa et al.

, 2003 ) . Many surveies have since been carried out to find whether the degree of PON1 activity in an person may find possible susceptibleness to organophosphate exposure ( Manthripragada, 2010 ; Chia et al.,2009 ; Costa et al.

, 2005 ) , nevertheless no conclusive consequences have been achieved.Atherogenesis is the status in which the intima beds of arterias bit by bit thickens, taking to decreased snap, narrowing and decreased blood circulation throughout the organic structure ( Matsuura et al. , 2006 ) . As atherogenesis have been attributed to oxidative alteration of LDL in the arterial walls ( Mackness et al. , 1999 ) , PON1 plays of import anti-atherogenic functions by supplying LDL protection against lipid oxidization by lipid hydroperoxides ( Adachi & A ; Tsuijimoto, 2006 ) . As oxidized phospholipids have been indicated to trip adhesion of monocytes to endothelium, a cardinal event in the pathogenesis of coronary artery disease, early remotion of these oxidised lipid byproducts may forestall the development of coronary artery disease ( Heinecke & A ; Lusis, 1998 ) . The hydrolytic active sites of PON1 have besides been shown to lend to the stimulation of HDL-mediated macrophage cholesterin outflow ( Rosenblat et al. , 2006 ) .

Increased cholesterin outflow therefore prevents deposition of cholesterin in the arterial wall, a procedure which contributes to the acceleration of coronary artery disease development ( Esparragon et al. , 2006 ) . Therefore, the function of PON1 is clearly protective against coronary artery disease through its antioxidant consequence towards lipid oxidization of both LDL and HDL, in add-on to its stimulatory consequence towards HDL-mediated cholesterin outflow.

Substrates of PON1

As stated earlier, PON1 has been associated with a broad scope of substrates, runing from active metabolites of organophosphates to oxidized lipoids such as lipid peroxides. However, the physiological substrate still remains to be known with probes still ongoing ( Ng et al. , 2005 ) . Recent grounds have shown have identified a scope of lactones including 5-hydroxyeicosatetraenoic acid lactone ( Teiber et al.

, 2006 ) and homocysteine thiolactone ( Kosaka et al. , 2005 ) and besides H peroxide ( Aviram et al. , 1998b ; Karabina et al. , 2005 ) as possible campaigners for PON1 hydrolysis.

Variation in PON1 Activity

It has been known for some clip that PON1 activity extremely fluctuates, changing by 13- up to 40-folds among persons in a given population ( Davies et al. , 1996 ; Richter & A ; Furlong, 1999 ) . Although the mechanism of PON1 activity look is non good described, surveies of PON1 cistron look have found that PON1 booster polymorphisms, particularly that of 192QR, 55LM and -108CT may account for up to 25 % of fluctuation in serum PON1 degrees ( Leviev & A ; James, 2000 ) .

The remainder of the fluctuation may be accounted for by a great figure of other factors, both environmental and biological ( Costa et al. , 2005 ) .

PON1 Q192R Polymorphism

Although there at least 198 known single-nucleotide polymorphism ( SNPs ) in the human PON1 cistron ( La Du, 2003 ) , most of the fluctuation of PON1 activity are influenced by three common polymorphism sites ; the 55LM, 192QR and -108CT polymorphism sites. The 55LM and 192QR polymorphism is located at Exons 3 and 6 severally, while -108CT polymorphism is found in the regulative parts of the cistron ( Durrington et al. , 2001 ) .Among these, the 192QR polymorphism was found to be the most of import with the wild-type Q allelomorph associated with low paraoxonase ( POase ) activity ( Mueller et al. , 1983 ) . The PON1 192R allelomorph perchance improves the placement of paraoxon on the active site, thereby bring forthing a more effectual hydrolysis and higher activity ( Harel et al.

, 2004 ) . However, the opposite is true for the hydrolysis of nervus agents and oxidized HDL or LDL with PON1 192Q allelomorph being more efficient at metabolizing those substrates.

PON1 Status

Many surveies have been carried out on the association of PON1 with diseases, nevertheless most have merely examined the most common nucleotide polymorphisms nowadays. However, such analysis does non supply the complete image of the degrees of plasma PON1 activity even if all polymorphisms present in PON1 cistron were tested.

This is due to the high fluctuation of PON1 activity expressed and besides the many modulating factors, both biologically and environmentally. Therefore, a functional genotype analysis would supply much more information as measurings of plasma PON1 activity takes into history all polymorphisms and other factors which might hold affected the uttered activity ( Costa et al. , 2005 ) .

Such an attack have been referred to as the finding of PON1 position, which takes into history the measuring of PON1 activity coupled with PCR genotying of codon 192 to place any possible disagreements due to possible undiscovered mutants in the PON1 cistron ( Richter & A ; Furlong, 1999 ) . For this survey, the finding of PON1 position was carried out utilizing a two-substrate method as described by Richter et al. , 2004 ) .

Oxidative Stress

Free groups are molecules which are characterised by the presence of one or more odd negatrons. Being odd, there negatrons are extremely reactive as they continuously attempts to partner off up with other molecular constructions to accomplish a more stable province. Therefore, these free extremist species can respond with most cellular supermolecules, altering molecular constructions and finally modifying the cellular maps of the cell ( Wu & A ; Cederbaum, 2003 ) .

Due to its critical function in the respiratory concatenation of all life beings, O has normally been associated with free extremist formation, organizing reactive O species ( ROS ) such as superoxides ( O2aˆ?- ) , hydroxyls ( aˆ?OH ) , hydroperoxyls ( HOOaˆ? ) and alkoxyls ( ROaˆ? ) ( Evans & A ; Halliwell, 2001 ) .As free groups are being formed invariably through metabolic maps, cells have adapted protective mechanisms to detoxicate these free groups before any harm is done to the cells ( Wu & A ; Cederbaum, 2003 ) . These protective mechanisms are most likely to affect antioxidants, which are any substances which are able to significantly hold-up or keep the oxidization of a substrate, when nowadays in low sums relative to the oxidised substrate ( Halliwell & A ; Gutteridge, 1989 ) . Antioxidants may be present in two signifiers, whether enzymatic or non-enzymatic in nature and they act by three chief mechanisms ; forestalling the production of free groups, ending the free group concatenation reaction and mending the harm caused by free groups ( Sies, 1993 ) .When there exist an instability between free groups and antioxidants which fall in favor of free groups, there is a potency of terrible cellular harm caused by free groups and this status is known as oxidative emphasis ( Sies, 1985 ) .

Many surveies have shown that a province of oxidative emphasis can take to weave harm ( Sies, 1997 ) and perchance play of import functions in the aetiology of many diseases ( Brownlee, 2001 ) .

Oxidative Stress in the Human Cornea

As described earlier, the cornea protects the interiors of the oculus from environmental injuries. However, by making so the cornea itself is invariably exposed to harmful elements such as UV ( UV ) radiation, which have been reported widely as an environmental emphasis factor which contributes to the formation of free groups in most cells and tissues ( Wenk et al. , 2001 ) . As the cornea absorbs most of the UV radiation come ining the oculus, it is most likely that the cornea is particularly predisposed to amendss from ROS. Surveies have reported of assorted antioxidant enzymes present in the cornea, such as aldehyde dehydrogenase ( ALDH3 ) , superoxide dismutase ( SOD ) , catalase, glutathione peroxidise and glutathione reductase, all of which contribute to the remotion of ROS in the cornea. ( Abedinia et al.

, 1990 ; Rao et al.,1987 ) .

Oxidative Stess in Keratoconus

Many surveies have been carried out on the function of oxidative emphasis in KC cornea.

A survey on oxidative emphasis degrees in human corneal diseases found accretion of cytotoxic byproducts from both lipid peroxidation and azotic oxide tracts of oxidative emphasis in KC corneas. From these findings, it was suggested that KC corneas do non treat the ROS in a similar mode to healthy corneas, which could hold contributed to the pathogenesis of KC ( Buddi et al. , 2002 ) . Other surveies have found reduced degrees of of import corneal antioxidant enzymes in KC cornea, such as ALDH3 ( Gonghowiardjo et al. , 1993 ) , SOD ( Behndig et al. , 1998 ) and catalase ( Kenney et al. , 2005 ) , an enzyme responsible for H peroxide hydrolysis.

When taken together, the deficiency of these enzymes in KC corneas have significantly increased accretion of malonaldehyde ( MDA ) from lipid peroxidation tracts and nitrotyrosine ( NT ) from azotic oxide tracts. Therefore, all of these findings have led to a on the job hypothesis, the “ Cascade Hypothesis ” which states that KC corneas may hold an implicit in defect in their ability to detoxicate ROS and therefore suffers from oxidative harm that triggers a cascade of events which finally lead to corneal cutting ( Kenney & A ; Brown, 2003 ) .

Oxidative Stress and PON1

As stated earlier, PON1 have been showed to play an of import antioxidant function in protection against coronary artery disease through its action of forestalling lipid oxidization of both LDL and HDL molecules. PON1 have besides been shown in assorted surveies to be able to neutralize the toxic effects of lipid peroxides. As a recent survey have found look of PON1 mRNA human cataractous lens which was expected due of the widely recognized function of PON1 as an antioxidant enzyme ( Hashim et al. , 2009 ) , there is a high possibility of PON1 holding the same antioxidant function in the cornea. Therefore, this survey hypothesized that there would be decreased PON1 activity due to the presence of oxidative emphasis in KC cornea.

Justification of This Survey

Although there have been studies of KC developing in babies and besides in persons every bit tardily as the age of 51 old ages, the bulk of KC patients develop this status between the ages of 12 to 20 old ages ( Hall, 1963 ) , which is around the oncoming of pubescence.

It is truly lay waste toing for one to develop such a status at this point in life, when 1 is still immature and motivated. In Malaysia, the prevalence of KC appears low with studies of approximately 4 in 1169 ( 0.3 % ) in a population of oculus patients in an urban country and 0.3 % among school-aged kids ( Reddy et al. , 2008 ; Goh et al. , 2005 ) . However, due to the hard nature of naming KC in its different developmental phases, many instances frequently go undetected until after multiple ailments from the patient and after thorough analysis of the patient ‘s vision sharp-sightedness trial consequences ( Benjamin, 2006 ) .

Therefore, the prevalence of KC in the general Malaysian population could be much higher than reported. As KC is reported as among the top five treatable causes of sightlessness and terrible ocular damage in kids in Malaysia ( Reddy, 2001 ) , more attempt should be carried out to plan effectual and accurate sensing checks utilizing the promotion of molecular medical specialty to supply early intervention to these persons before the status worsen.


The aims of this survey are as follows:To find forecasters of KC position and POase activity from pooled informationsTo find PON1 activity and position in KC patients and to compare with non-KC controls.To find the strength of the association between KC and POase activity and place possible confounders to this association, if any.


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