Retinal damage is one of the most common causes of blindness in the modern world. About 5% of the world population suffers from retinal damage at some time point in their lifetime. Though we have made remarkable progress with regard to the treatment of retinal damage, efficient strategies for repairing damaged retina still remains elusive. Various mammalian, avian and piscine animal model studies have revealed the potential of a cell type called Muller glia (MG) in the restoration of vision after an acute damage in the retina. However the piscine model zebrafish offers the maximum potential in unraveling the mystery of retinal regeneration compared to its mammalian or avian counterparts. Though the retina regeneration in zebrafish is a known fact, the exact mechanism remained largely unknown. The success of implementing the lessons learned from lower vertebrates into human-benefit and treatment exclusively depend on unraveling the mystery of retinal regeneration. Apart from this, the retina being part of central nervous system, the regenerative potential of the neurons in the retina can give immense clues about various signaling mechanisms that lead to restoration of neural circuitry after an acute injury.
My research interests are to understand the molecular mechanisms underlying retina regeneration using zebrafish model. Though the cellular and molecular basis of this remarkable phenomenon remains largely unknown, recent studies have suggested the detrimental role of various genetic factors like hb-egfa, ascl1a, lin28, and pax6b in fish retina regeneration. However, the wealth of knowledge is not sufficient to take this to the next stage, where humans can get benefited out of this. In this scenario, I am working on signaling pathways like wnt, notch and hedgehog to assess their impact on fish retina regeneration. I am also working on a few selected candidate genes like pluripotency inducing factors like sox2, oct4, nanog, klf4, cMyc and lin28 involved in retina regeneration.
- Ramachandran, R, Zhao, X-F, Goldman, D. (2012). Insm1a-mediated gene repression is essential for the formation and differentiation of Müller glia-derived progenitors in the injured retina. Nat. Cell Biol. 14: 1013-1023.
- Wan, J, Ramachandran, R, Goldman, D. (2012). HB-EGF Is Necessary and Sufficient for Muller Glia Dedifferentiation and Retina Regeneration. Dev. Cell 22: 334-347
- Ramachandran, R, Zhao, X-F, Goldman, D. (2011) An Ascl1a/Dkk/β-Catenin signaling pathway is necessary and glycogen synthase kinase-3β inhibition is sufficient for zebrafish retina regeneration. Proc. Natl. Acad. Sci. USA 108: 15858-15863.
- Ramachandran R, Fausett B V, Goldman D (2010). Ascl1a regulates Muller glia dedifferentiation and retinal regeneration through a Lin-28-dependent, let-7 microRNA signalling pathway. Nat. Cell Biol. 12: 1101-1107
- Ramachandran R, Reifler A, Parent JM, Goldman D (2010). Conditional gene expression and lineage tracing of tuba1a expressing cells during zebrafish development and retina regeneration. J. Comp Neurol. 518:4196-212.