Vision restoration with photoswitch technology

描述（由申请人提供）：色素性视网膜炎（RP）是一种遗传性眼睛疾病，使患者丧失视力。视力的丧失是由于视网膜的视杆细胞和视锥细胞退化引起的，而视网膜上的其他细胞仍然存活。RD是一种相对罕见的疾病，在美国大约有10万人受到影响。盲校中大约20%的儿童患有视网膜萎缩症。显然，RP的灾难性后果为深入研究其原因和潜在的治疗方法提供了理由。由于RP的多基因性质，它不适合基因治疗或靶向治疗。尽管有报道称基因疗法在视力恢复方面取得了一些成功，但这种疗法在不久的将来被医学界批准和采用的可能性很小。在第一阶段的SBIR应用中，提出了一种不涉及基因治疗的RP患者视力恢复的替代方法，即使用称为“光开关”的小分子将受损视网膜中的剩余细胞制成光敏细胞。从理论上讲，光开关提供的分辨率大约是竞争对手摄像机假肢的一千倍，而且侵入性要小得多。在获得批准的治疗途径的第一步中，有四个具体目标：(1)通过将光开关注射到失明小鼠的眼睛中，确定视网膜中许多细胞中的哪些细胞具有光敏性；(2)利用非侵入性电生理方法证明完整突变盲小鼠的光敏性；(3)基因盲小鼠在光开关处理后表现出光依赖行为；(4)确定维持突变盲小鼠光敏性的最佳参数。这个可行性项目的成功完成将为进一步追求这种治疗失明的方法提供理由。

DESCRIPTION (provided by applicant): Retinitis Pigmentosa (RP) is an inherited disease of the eye that robs its victims of vision. The loss of vision is caused by the degeneration of the rods and cones of the retina while other cells in the retina remain alive. RD is a relatively rare disease, affecting approximately 100,000 people in the US. Approximately 20% of children in schools for the blind suffer from RP. Clearly, the disastrous consequences of RP provide justification for intense research into the causes and potential therapies. Due to the polygenic nature of RP, it does not lend itself to gene therapy or targeted therapeutics. Although some successes in vision restoration using gene therapy have been reported, it is highly unlikely that such therapy will be approved and adopted by the medical community in the near future. An alternative approach to vision restoration for patients with RP, which does not involve gene therapy, is proposed in this Phase I SBIR application where the remaining cells in the damaged retina are made into photosensitive cells using small molecules called "photoswitches". Photoswitches could, in theory, provide resolution approximately a thousand times greater than that of competing video camera prosthetics and will be far less invasive. The four Specific Aims for the first steps along the pathway to an approved therapeutic are (1) Determine which of the many cells in the retina are rendered light-sensitive by the injection of photoswitches into the eyes of blind mice; (2) Demonstrate light-sensitivity in intact mutant blind mice using non-invasive electrophysiological approaches; (3) Demonstrate light-dependent behavior in genetically blind mice after photoswitch treatment; and (4) Determine the optimal parameters for maintaining light-sensitivity in mutant blind mice. The successful completion of this feasibility project will provide justification for the further pursuit of this therapeutic approach to blindness. PUBLIC HEALTH RELEVANCE: Retinitis Pigmentosa (RP) is an inherited disease of the eye that robs its victims of vision. While RD is a relatively rare disease, affecting approximately 100,000 people in the US, approximately 20% of children in schools for the blind suffer from RP. Clearly, the disastrous consequences of RP provide justification for intense research into the causes and potential therapies. Photoswitch Biosciences has developed a technology that has the potential to make healthy cells in the eye into cells that can receive and decode light, restoring sight to sufferers of RP.