Retinopathy of Prematurity: Genetic Susceptibility and Clinical Application

Amartya Dutta, Bachelor of Optometry

Clinical Optometrist, Lokeswarananda Eye Foundation, Purulia

 

What is Retinopathy of Prematurity (ROP)?

Retinopathy of prematurity (ROP) is a form of visual derangement encountered among premature babies. The majority of such infants are short for gestational age (SGA) and often low birthweight (LBW). This condition is said to be multifactorial which means that both genetic as well as environmental factors play a definitive role in its etiology (Bizzarro et al., 2006).

Pathogenesis of ROP

ROP is marked by the premature impairment of vascularization in the peripheral parts of retina. This is followed by an extra-retinal proliferation of fibrovascular tissues while the result is mainly vitreal traction and retinal detachment. This makes it one of the most prevalent conditions underlying blindness in the newborn with up to 50,000 cases being reported worldwide annually.

Genetic Background of ROP

Recent clinical and experimental studies have shown a strong genetic predisposition to ROP where researchers have concluded that a higher percentage of such cases occurs among monozygotic twins (Shastry, 2010). This genetic background of ROP has also been described in terms of gender and racial characteristics.

1) Gender and Racial Background

A few researchers have found male sex to be an independent risk factor for ROP. Other studies have reported that although male gender may not be a significant etiological factor, it may well be associated with a higher severity of the disease among premature infants. From a racial perspective, ROP is predominantly seen among the infants of Asian descent, and several studies have reported these findings. On the contrary, it is less encountered among the African American and Caucasian communities, while the former is the least likely to be affected.

2) Genetic Mediators of ROP

In the patients diagnosed with ROP, mutations are found to involve four different sets of genes (Ortega-Molina et al., 2015):

1. Norrin (NDP)
2. BDNF variants (growth factor associated with the central nervous system)
3. Low density lipoprotein receptor-related protein (LRP5)
4. Frizzled family receptors (FZD4)

3) Growth Factors in ROP

Besides these rare mutations, genetic polymorphisms have also been documented within the genes such as vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF-1). VEGF is widely held responsible for controlling the process of angiogenesis (generation of new vessels). Abnormal genetic variants of VEGF have been isolated in the retinal environment which constitute an independent risk factor in the pathogenesis of ROP. IGF-1 contributes to the physical growth and development of the human body. Reliable data have revealed that its deficiency can remarkably potentiate the pathogenesis of ROP (Holmström, van Wijngaarden, Coster, & Williams, 2007).

Clinical Application

The knowledge regarding genetic susceptibility towards ROP is still in the developing phase. The geneticists are contributing to the identification of several novel genetic polymorphisms and aberrations, a key step which could be a game-changer in infant ophthalmology care. In near future, it could become possible to identify those subjects who carry such genetic variants and are at a potentially higher risk for ROP. This would eventually help with the screening, surveillance, and management of the high-risk infants while contracting the potential risk of blindness associated with ROP (Holmström et al., 2007).

 

References

1. Bizzarro, M. J., Hussain, N., Jonsson, B., Feng, R., Ment, L. R., Gruen, J. R., . . Bhandari, V. (2006). Genetic susceptibility to retinopathy of prematurity. Pediatrics, 118(5), 1858-1863. doi:10.1542/peds.2006-1088
2. Holmström, G., van Wijngaarden, P., Coster, D. J., & Williams, K. A. (2007). Genetic susceptibility to retinopathy of prematurity: the evidence from clinical and experimental animal studies. Br J Ophthalmol, 91(12), 1704-1708. doi:10.1136/bjo.2007.117283
3. Ortega-Molina, J. M., Anaya-Alaminos, R., Uberos-Fernández, J., Solans-Pérez de Larraya, A., Chaves-Samaniego, M. J., Salgado-Miranda, A., . . . García-Serrano, J. L. (2015). Genetic and Environmental Influences on Retinopathy of Prematurity. Mediators of Inflammation, 2015, 764159. doi:10.1155/2015/764159
4. Shastry, B. S. (2010). Genetic susceptibility to advanced retinopathy of prematurity (ROP). Journal of Biomedical Science, 17(1), 69. doi:10.1186/1423-0127-17-69