Research Projects

The alarming rate of increase in diabetes among young individuals has made Diabetic Retinopathy (DR) a major threat to vision. There are treatments available for DR but they are very painful, expensive, not equally effective in all the patients and some patients even don’t respond to the treatment. Also, the current treatment strategies don’t focus on the early stage of the disease. The metabolic memory phenomena associated with diabetes and the fact that DR remains asymptomatic during its initial stage are the major cause of concern. By the time the symptom appears, some vision loss has already taken place which cannot be compensated. Hence, the need to find early diagnosis and treatment strategies are of prime importance. An ample of studies has shown the role of epigenetic modifications, especially DNA methylation in the formation of metabolic memory. While evidences from various studies show the neurodegeneration to be one of the earliest events occurring in the eye of diabetic. In the previous studies, we have reported the nine crucial genes have been altered during the early stage of DR (Kumari et al., 2020). Among them, the Immunoglobin Superfamily Member 21(IGSF21) has a vital role in the physiological function of neuroretinal cells, although only limited information are available about its pathological role in DR. Our preliminary work suggests increased expression of IGSF21 in retinal pigmented epithelial cells and glial cells in vitro. Also, the single-cell analysis revealed that in the diabetic retina, the expression of IGSF21 is very high in bipolar cells, followed by glial cells. (Fig. 1 & 2). Further, many studies have shown that the zebrafish can not only act as a model for DR but also has several advantages over the mostly used rodent DR model. Hence, considering the above points, we propose to study the early events occurring during the DR pathogenesis by developing a zebrafish model. Our main focus will be to determine the altered IGSF21 gene DNA methylation pattern during an early stage of DR and its impact on neurodegeneration and metabolic memory phenomena. The potential therapeutic effect of DNA methyltransferase inhibitor (DNMTi) will also be determined. The study will help in understanding the early pathological events of DR and thus providing a way towards early DR treatment strategies.