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

高眼压常表现为青光眼，最终由于视网膜神经节细胞退化而导致失明。虽然许多研究集中在预防高眼压或研究保护神经节细胞免于变性的潜在方法，但相对较少的研究研究了刺激神经节细胞再生的可能性。一些动物在失去神经节细胞后能够再生新的神经节细胞。鱼类和两栖动物几乎可以完美地再生视网膜，并恢复高度的正常功能。不幸的是，哺乳动物（包括人类）不具备这种能力，因此当视网膜神经节细胞在青光眼等退行性疾病中丢失时，这些神经元永远不会恢复。总体目标是发现限制哺乳动物再生的分子和细胞障碍，着眼于重新启动这一过程以治疗各种类型的视网膜变性。本申请中提出的实验代表了确定刺激哺乳动物视网膜中存在的非常小的修复以产生新的视网膜神经节细胞的可行性的第一次尝试。Reh教授的研究小组发现，眼内注射生长因子的适当时机和组合可以恢复通过实验性神经毒素治疗鸡视网膜而丢失的一些神经节细胞。这些实验可能会告诉我们，我们是否可以在哺乳动物视网膜中使用相同的方法，并为开发治疗青光眼的新疗法奠定基础。

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.