Analysis of Mutations in Vsx1 Gene in Keratoconus Patients



Keratoconus is a degenerative non-inflammatory disorder of the eye leading to progressive thinning and steepening of the central cornea, changing it to a more conical shape than its normal gradual curve. The course of the disorder is variable. The patient suffers from blurred vision, myopia, astigmatism etc. It is a major cause of corneal transplants in the western world. Keratoconus affects around one person in a thousand and occurs in populations throughout the world. This progressive condition often onsets during the teenage years or early twenties with decreased vision. Studies reveal that over 5 lakh people suffer from this disease in India. Genetic factors are known to play a role in its causation. A positive family history has been found in 6% to 10% of the patients. Keratoconus shows an autosomal dominant mode of inheritance. It has been found in all races and in both sexes but found to affect women more often than males. VSX1 homeobox gene encodes transcription factors implicated in the control of corneal development. Recent studies suggest that mutations in the VSX1 homeobox gene might be associated with Keratoconus.


In the present study, VSX1 gene will be screened for the possible presence of mutations in the Keratoconus patients.


Blood samples will be collected from ten Keratoconus patients and ten unaffected individuals (controls). The sample will be subjected to DNA isolation followed by PCR to amplify DNA. The DNA will then be screened for possible mutation by SSCP.

Diagnosis of Keratoconus

Keratoconus can be difficult to detect, because it usually develops so slowly. However, in some cases, it may proceed rapidly. As the cornea becomes more irregular in shape, it causes progressive nearsightedness and irregular astigmatism to develop, creating additional problems with distorted and blurred vision. Glare and light sensitivity also may be noticed. The typical patient with undiagnosed Keratoconus complains of deteriorating vision, usually in one eye first, both at distance and near. Near visual acuity may improve if the patient squints or holds printed material closer. Keratoconus patients often report multiple images or ghosting of images and often relate a history of frequent refractive correction changes without much improvement in visual acuity.

Patients may also report irritating symptoms such as intolerance to glare, photophobia and a recurrent foreign body sensation. Identification of moderate or advanced Keratoconus is fairly easy. However diagnosing Keratoconus in its early stages is far difficult. Often Keratoconus patients have several spectacle prescriptions in a short period, and none has provided satisfactory vision correction. Keratoconus patients often report monocular diplopia or polyopia and complain distortion rather than blur or both distance and near vision.

The other several ways through which we can identify Keratoconus are the

• Retinoscopy shows an irregular ‘scissor’ reflex

• Fleischer ring which may or may not surround the base of the cone completely,

• Lines of Vogt which are small vertical brush like lines in the deep layer of Keratoconic stroma,

• Significant thinning (up to 1/5th cornea thickness) can be observed in the advanced stages of the disease,

• Sub-epithelial corneal scarring may occur as the progress of the disease because of the ruptures in Bowman’s membrane which is filled with connective tissues,

• Thickening of corneal nerves make them more visible

• Swirl staining may appear in patients who have never worn contact lenses because basal epithelial cells drop out and the epithelium slides from the periphery as the cornea regenerates.

• Corneal hydrops occurs, generally in advance cases, when Descemets membrane ruptures, aqueous flows into the cornea, and reseals.

• A low intraocular pressure is generally found which is the resulted from the thinning of cornea.

• Corneal protrusion causing bulging of the lower lid on downgaze (Munson sign)

Causes Of Keratoconus

Although progress had been made in understanding the molecular mechanisms of many corneal dystrophies, Keratoconus remains largely unexplained. Research suggests the weakening of the corneal tissue that leads to Keratoconus may be due to an imbalance of enzymes within the cornea. This imbalance makes the cornea more susceptible to oxidative damage from compounds called free radicals, causing it to weaken and bulge forward. Risk factors for oxidative damage and weakening of the cornea include a genetic predisposition, explaining why Keratoconus often affects more than one member of the same family. The frequency of occurrence in close family members is not clearly defined, though it is known to be considerably higher than that in the general population, and studies have obtained estimates ranging between 6% and 19%.

Corneal dystrophies, all of which have a genetic basis, are almost universally bilateral. Most patients with Keratoconus have bilateral disease. (In many instances the disease may initially be unilateral, but over time the contra lateral eye becomes involved). This bilateral nature of Keratoconus, similar to that of corneal dystrophies, strongly suggests that Keratoconus has a genetic basis. But a responsible gene has not been identified yet Keratoconus is also associated with overexposure to ultraviolet rays from the sun, excessive eye rubbing, a history of poorly fit contact lenses, and chronic eye irritation. Studies have revealed that VSX1 gene on chromosome 20 help convert naturally occurring but harmful superoxide radicals to molecular oxygen and water to exhibit autosomal dominant inheritance.

VSX1 Gene

The protein encoded by VSX1 gene contains a paired-like homeodomain and binds to the core of the locus control region of the red/green visual pigment gene cluster. The encoded protein may regulate expression of the cone opsin genes early in development.

Highlights of the Project

Keratoconus is an eye disorder where in the cornea becomes thin and gradually cone shaped leading to visual distortion. Keratoconus cases account for approximately 1 in 2000 general population. Around 5% of the cases of the disease show familial history following mode of inheritance. Most Keratoconus cases are found to have an approximate onset in the teenage. Genetic factors have been implicated in the inheritance of Keratoconus.






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