[Frontiers in Bioscience 11, 908-920, January 1, 2006]

Pathogenesis and genetic basis for retinopathy of prematurity

Krisztina Csak 1, Viktoria Szabo 2, Andras Szabo 3, Adam Vannay 3

1 Department of Family Medicine, Semmelweis University, Budapest, Hungary, 2 Department of Ophthalmology, Semmelweis University, Budapest, Hungary, 3 1st Department of Paediatrics, Semmelweis University and Research Group for Paediatrics and Nephrology, Hungarian Academy of Scineces, Budapest, Hungary


1. Abstract
2. Introduction
3. Pathogenesis
4. Classification
5. Treatment
6. Genetic background
6.1. Polymorphism of Norrie disease gene
6.2. Polymorphism of VEGF gene
6.3. Polymorphism of ACE, TGF beta-1 and TNF alpha, gene
6.4. Summary
7. Perspectives
8. Acknowledgements
9. References


Retinopathy of prematurity (ROP) is a vasoproliferative disorder affecting preterm infants with low gestational age and birth weight. In general more than 50 % of preterm infants weighing less than 1250 g at birth show evidence of ROP and about 10 % of the infants develop stage 3 ROP. However, retinal detachment occurs and leads to visual loss in only a few percent of infants with stage 3 or more severe ROP, and in most cases, spontaneously regresses. The most conspicuous question is why ROP in some premature infants progresses despite rigorous and timely intervention while in other cases with similar clinical characteristics it regresses. Genetic differences between the infants could be an explanation. Although many causative factors, like low birth weight, low gestational age and supplemental oxygen therapy are associated with ROP, several indirect lines of evidence suggest the role of a genetic component in the pathogenesis of ROP. The incidence of ROP is more frequent in white than in black infants and in males than in females. Genetic polymorphism may alter the function of the genes which normally control retinal vascularization, such as vascular endothelial growth factor (VEGF), which may also be involved in pathogenesis of ROP. Evaluation of candidate genetic polymorphism influencing the outcome of ROP may provide new information about the pathogenesis of the disease. Screening of genetic polymorphisms may also help to identify and treat the high risk infants in time.