In the retina, death of photoreceptors due to injury or disease leads to irreversible loss of vision. Loss of photoreceptors is often followed by destructive remodeling of the inner retinal layers that leads to abnormal retinal structure and function. Recently, it has been discovered that selective destruction of a small patch of photoreceptors leaving the inner-retinal neurons intact, leads to migration of the photoreceptors from outside of the lesioned area into the lesion over the period of a few months, thereby restoring retinal continuity. Our pilot data shows that as a result of this process retinal sensitiity in the initial blind spot introduced by photocoagulation can be restored. Moreover, our observations indicate that migrating photoreceptors establish new synaptic connections with bipolar cells in the lesion. These findings demonstrate that retina has the potential for constructive plasticity never observed or even suspected before. Our goal is to establish the mechanism and the limits of this new exciting phenomenon. In particular, the main hypothesis we propose to test is that the healthy photoreceptors migrate inside the lesion and establish new and appropriate connections to the deafferented retinal circuitry inside the lesion. We will test this hypothesis by characterizing functional and anatomical changes induced by selective photocoagulation through multielectrode array recordings of retinal activity and antibody labeling of various retinal neuronal types and synapses. The phenomenon of the constructive retinal plasticity becomes an extremely useful model for understanding the mechanisms of the development of the intricate and specific retinal connectivity in the adult mammalian retina. Of immediate clinical importance is that the results of the proposed research will enable development of novel approach to retinal photocoagulation that will avoid deleterious side effects of the current standard of care, such as scotomata and scarring. Retinal photocoagulation is widely used to treat various retinopathies and its improvement will affect millions of patients worldwide. Results of the research may also provide insights into processes of functional integration of transplanted photoreceptors or stem cells into the adult retina.
In the retina, death of photoreceptors due to injury or disease often leads to irreversible loss of vision. We will investigate the newly discovered phenomenon of photoreceptors migration and rewiring that may enable restoration of visual function in retinal lesions. This new phenomenon has crucial implications for development of novel approach to retinal photocoagulation that will avoid deleterious side effects of the current standard of care, such as scotomata and scarring and will also provide insights into processes of functional integration of photoreceptors or stem cells transplanted into the adult retina.
|Lorach, H; Kang, S; Dalal, R et al. (2018) Long-term Rescue of Photoreceptors in a Rodent Model of Retinitis Pigmentosa Associated with MERTK Mutation. Sci Rep 8:11312|
|Beier, Corinne; Hovhannisyan, Anahit; Weiser, Sydney et al. (2017) Deafferented Adult Rod Bipolar Cells Create New Synapses with Photoreceptors to Restore Vision. J Neurosci 37:4635-4644|
|Sher, Alexander; Jones, Bryan W; Huie, Philip et al. (2013) Restoration of retinal structure and function after selective photocoagulation. J Neurosci 33:6800-8|