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.
- Soumitra Mitra, Poonam Sharma, Simran Kaur, Mohammad Anwar Khursheed Shivangi Gupta, Riya Ahuja, Akshai Janardhana Kurup, Mansi Chaudhary, and Rajesh Ramachandran (2018). Histone Deacetylase-Mediated Muller Glia Reprogramming Through Her4.1-Lin28a axis is Essential for Retina Regeneration in Zebrafish. iScience 7: 68-84.
- Simran Kaur, Shivangi Gupta#, Mansi Chaudhary#, Mohammad Anwar Khursheed Soumitra Mitra, Akshai Janardhana Kurup and Rajesh Ramachandran (2018). let-7 MicroRNA-Mediated Regulation of Shh Signaling and the Gene Regulatory Network Is Essential for Retina Regeneration. Cell Reports 23: 1409-1423.
- Rajesh Ramachandran, Xiao-Feng Zhao, Daniel Goldman (2012). Insm1a-mediated gene repression is essential for the formation and differentiation of Muller glia-derived stem cells in the injured retina. Nature Cell Biology 14: 1013-1023.
- Rajesh Ramachandran, Xiao-Feng Zhao, Daniel Goldman (2011). An Ascl1a/Dkk/β-Catenin signaling pathway is necessary and glycogen synthase kinase-3β inhibition is sufficient for zebrafish retina regeneration. Proceedings of the National Academy of Sciences, USA 108: 15858-15863.
- Rajesh Ramachandran, Blake Fausett and Daniel Goldman (2010). Ascl1a regulates Müller glia dedifferentiation and retina regeneration via a Lin28-dependent, let-7 miRNA signaling pathway. Nature Cell Biology 12: 1101-1107.