[Frontiers in Bioscience 11, 908-920, January 1, 2006] 908 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 1 st Department of Paediatrics, Semmelweis University and Research Group for Paediatrics and Nephrology, Hungarian Academy of Scineces, Budapest, Hungary TABLE OF CONTENTS 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 1. ABSTRACT 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. 2. INTRODUCTION Retinopathy of prematurity (ROP) is a leading cause of impaired vision and blindness in children throughout the world. It is a retinal vascular disease that occurs in infants with low gestational age and birth weight (1, 2). ROP is characterized by retinal neovascularisation, which possibly leads to retinal detachment, macular folds, myopia, refractive amblyopia, or strabismic amblyopia and may result in visual loss or blindness (3-8). ROP is becoming more frequent due to the improved survival of extremely premature infants (9). Several etiologic factors including exposure to oxygen have been implicated in the pathogenesis of ROP. Although the exact mechanism of ROP is not yet fully understood, indirect lines of evidence suggest the possible role of a genetic component. Genetic factors such as polymorphisms of different genes may alter not only the risk but also the progression of ROP (11-15). Monitoring of the genetic factors may help to identify infants with a high risk of advanced ROP. The CRYO-ROP randomized controlled trial demonstrated that early detection followed by cryotherapy or laser photocoagulation treatment may decrease the incidence of adverse structural outcome and visual loss by approximately 50 % (2).