Replacement of ganglion cells through regeneration - structural and functional analysis of cell integration

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The ocular hypertension that frequently characterizes glaucoma, ultimately causes blindness because retinal ganglion cells degenerate. Although many studies have focused on prevention of ocular hypertension or investigated potential ways to protect ganglion cells from degeneration, relatively few studies have investigated the possibility of stimulating ganglion cell regeneration. Some animals are capable of regenerating new ganglion cells after they are lost. Fish and amphibians can regenerate their retinas almost perfectly and regain a high degree of normal function. Unfortunately, mammals (including humans) do not possess this capability, and so when the retinal ganglion cells are lost in degenerative disorders like glaucoma, these neurons are never restored. It is an overall goal to discover the molecular and cellular roadblocks that limit regeneration in mammals, with an eye towards re-initiating this process to treat various types of retinal degenerations. The experiments proposed in this application represent a first attempt to determine the feasibility of stimulating the very minimal repair that exists in the mammalian retina to produce new retinal ganglion cells. Prof. Reh´s group found that the appropriate timing and combination of intraocular injections of growth factors can restore some of the ganglion cells lost through experimental neurotoxin treatment in the chick retina. The experiments proposed might tell us whether we can use the same approach in the mammalian retina and serve as a foundation for developing new therapies for the treatment of glaucoma.