Genetic Predisposition to Advanced Retinopathy of Prematurity (ROP) Gains Support

Aims: The purpose of this short review is to summarize the recent developments in the genetics of retinopathy of prematurity.

Background: Retinopathy of prematurity is a well known blinding disorder in children in both developed and developing countries. It is characterized by the hypovascularization of the peripheral retina in children with a short gestational age and low birth-weight. Morphologically it is similar to familial exudative vitreoretinopathy (FEVR) but FEVR patients do not have the history of oxygen therapy and prematurity. ROP is a life time disease and patients can still have long-term effect even after timely treatment. Although many causative factors have been suggested, the pathogenesis of ROP is not understood. Some of the unpredictability of ROP could be due to genetic factors.

Methodology: Using the key words or phrases such as ROP, genetics, animal models and pediatric retinal disorders, the literature search was carried out.

Results: Molecular genetic analysis has identified mutations in three of the four FEVR causing genes in patients with advanced ROP in different ethnic backgrounds. These three genes are involved in a highly regulated Wnt signaling pathway that controls the development of the retinal vasculature. The genetic association of ROP was further supported by the higher concordance rate of the disorder in monozygotic twins, racial variation, strain dependent difference in oxygen-induced ROP in inbred rats and the existence of quantitative loci on chromosome 7 and 9 that modify susceptibility to oxygen-induced ROP.

Conclusion: Although much remains to be done in the field of ROP, the above finding supports a role for the Wnt signaling pathway in the development of severe ROP. The availability of animal models may provide opportunities for the development of novel therapeutic approaches to prevent or treat this pediatric blinding disorder.