Sudhakar and Sreekanth Ravi Stem Cell Biology Laboratory
The stem cell laboratory, set up with the generous support of two brothers - Sudhakar Ravi and Sreekanth Ravi of California, USA - is engaged in frontline research designed to apply knowledge of stem cell biology to the treatment of eye diseases. Stem cells, or undifferentiated cells from a donor eye, are cultured in a special medium to generate corneal cells that can then be transplanted into the eye of a person with corneal blindness. In the area of ocular surface damage, the laboratory has been particularly successful in developing a technique of culturing limbal stem cells ex-vivo on an amniotic membrane substrate and transplanting the resultant corneal epithelium into the patient's eye. The laboratory is also attempting to transdifferentiate stromal cells from the bone marrow into cells of neuronal lineage, which could then be taken further to grow retinal cells.
New stem cell initiatives to address retinal disorders
Investigators: Indumathi Mariappan, Chitra Kannabiran, D Balasubramanian, Geeta K Vemuganti, Virender S Sangwan, Subhadra Jalali, Annie Mathai, Raja Narayanan, Milind Naik
Support: Hyderabad Eye Research Foundation (LVPEI)
Retinal dystrophy is a progressive genetic disorder resulting in degeneration of rod and cone photoreceptor cells causing night blindness and gradual loss of vision, progressing to complete blindness. The most untreatable form of blindness is caused by the loss of rod and cone photoreceptor cells and the adjacent retinal pigment epithelial cells. Treatment modalities including gene therapy slow down disease progression by preventing or delaying further cell death, but the photoreceptors once lost cannot be salvaged. Therefore, cell replacement therapy holds a great promise in treating such diseases. Many studies have shown that retina is amenable for cell replacement therapy, initiating a search into adult stem cells that can give rise to photoreceptor cells and retinal-pigmented epithelial (RPE) cells.
The ciliary-pigmented epithelium (CPE) of the human eye is known to harbor retinal stem cells, which can differentiate into RPE cells and the retinal neurons including photoreceptor cells. Limbal stem cells (LSC) are more plastic and can be induced to express neural stem cell markers when cultured in the presence of mitogens and inhibitors of BMP signaling pathway. It has also been shown that completely differentiated adult somatic cells, like skin fibroblasts can be reprogrammed to a more primitive ES-like state by ectopic expression of some of the genes implicated in stemness and pluripotency. These cells were christened as induced pluripotent stem cells (iPSCs) and they behave very much similar to ES cells in terms of stemness and pluripotency.
LVPEI has initiated basic research towards isolation, characterization and differentiation of both CPE and LSCtowards retinal progenitor lineage for their possible use in cell replacement therapy. We have also initiated basic research towards the establishment of RP patient-specific iPS cells to check their potential to differentiate into retinal progenitors.