Genetic susceptibility to advanced retinopathy of prematurity (ROP)

Retinopathy of prematurity (ROP) is a vascular vitreoretinopathy that affects infants with short gestational age and low birth-weight. The condition is a multifactorial disease and is clinically similar to familial exudative vitreoretinopathy (FEVR), which is a bilateral hereditary eye disorder affecting full-term infants. Both of them are characterized by the abnormal vessel growth in the vitreous that can lead to vitreoretinal traction, retinal detachment and other complications resulting in blindness. Despite the recent advances in diagnosis and treatment, ROP remains a major cause of childhood blindness in developed countries. The etiology of pathogenesis of advanced ROP is currently unknown. In the past, many causative factors such as length of time exposed to supplemental oxygen, excessive ambient light exposure and hypoxia have been suggested but evidence for these as independent risk factors in recent years is not compelling. It is not clear why ROP in a subset of infants with low birth-weight progresses to a severe stage (retinal detachment) despite timely intervention whereas in other infants with similar clinical characteristics ROP regresses spontaneously. Recent research with candidate gene approach, higher concordance rate in monozygotic twins and other clinical and experimental animal studies, suggest a strong genetic predisposition to ROP besides environmental factors such as prematurity. Three genes, which are involved in the Wnt signaling pathway, are mutated in both FEVR and in a small percentage of ROP disorder. However, none of the genetic factors identified thus far in ROP, account for a substantial number of patient population. Future studies involving genomics, bioinformatics and proteomics may provide a better understanding of the pathophysiology and management of ROP

Genetic Susceptibility to Normal Tension Glaucoma (NTG)

Aims: The Purpose of this short article is to summarize the recent developments in the genetics of normal tension glaucoma (NTG). Background: Glaucoma is one of the leading causes of irreversible blindness. Primary open-angle glaucoma (POAG) is the most common type of glaucoma in most populations and is frequently associated with elevated intraocular pressure (IOP). However, patients with POAG can also have IOP within the normal range and they are classified as having normal tension glaucoma (NTG) – most likely an independent entity. In NTG, the optic nerve head is just susceptible to normal IOP. Therefore, factors other than elevated IOP are likely to play a role in the pathogenesis of glaucoma. Although factors such as myopia, older age, vasospasm, ischemia and vascular insufficiency are indicated to be associated with the development of NTG, substantial percentage of NTG patients (21%) have a family history of glaucoma suggesting that these patients may have a genetic predisposition for developing NTG. Methodology: Using the keywords or phrases such as glaucoma, genetics, normal tension glaucoma, open-angle glaucoma and retinal ganglion cell, the literature search was carried out. Results: NTG is a genetically complex disorder and many genes have been reported to be associated with the development of glaucoma. However, none of them account for a substantial portion of patient population. A complex glaucoma pathogenesis may include interplay among several factors such as genetic, epigenetic and environmental factors. Therefore, an understanding of IOP independent mechanisms of development of NTG is important. Conclusion: NTG is relatively a less explored avenue of research. There has been paucity of research into the genetic basis of NTG

Autosomal Recessive Familial Exudative Vitreoretinopathy Is Associated with Mutations in LRP5

Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disorder that affects both the retina and vitreous body. Autosomal recessive FEVR was diagnosed in multiple individuals from three consanguineous families of European descent. A candidate-locus–directed genome scan shows linkage to the region on chromosome 11q flanked by markers D11S905 and D11S1314. The maximum LOD score of 3.6 at θ=0 is obtained with marker D11S987. Haplotype analysis confirms that the critical region is the 22-cM (311-Mb) interval flanked by markers D11S905 and D11S1314. This region contains LRP5 but not FZD4; mutations in both of these genes cause autosomal dominant FEVR. Sequencing of LRP5 shows, in all three families, homozygous mutations R570Q, R752G, and E1367K. This suggests that mutations in this gene can cause autosomal recessive as well as autosomal dominant FEVR