CLN2 neuronal ceroid lipofuscinosis is a rare recessive hereditary retinal and neurodegenerative disease resulting from deleterious sequence variants in TPP1 that encodes the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Children with this disorder develop normally, but starting at 2–4 years of age begin to exhibit neurological signs and visual deficits. Vision loss that progresses to blindness is associated with progressive retinal degeneration and impairment of retinal function. Similar progressive loss of retinal function and retinal degeneration occur in a dog CLN2 disease model with a TPP1 null sequence variant. Studies using the dog model were conducted to determine whether intravitreal injection of recombinant human TPP1 (rhTPP1) administered starting after onset of retinal functional impairment could slow or halt the progression of retinal functional decline and degeneration. TPP1-null dogs received intravitreal injections of rhTPP1 in one eye and vehicle in the other eye beginning at 23.5–25 weeks of age followed by second injections at 34–40 weeks in 3 out of 4 dogs. Ophthalmic exams, in vivo ocular imaging, and electroretinography (ERG) were repeated regularly to monitor retinal structure and function. Retinal histology was evaluated in eyes collected from these dogs when they were euthanized at end-stage neurological disease (40–45 weeks of age). Intravitreal rhTPP1 injections were effective in preserving retinal function (as measured with the electroretinogram) and retinal morphology for as long as 4 months after a single treatment. These findings indicate that intravitreal injection of rhTPP1 administered after partial loss of retinal function is an effective treatment for preserving retinal structure and function in canine CLN2 disease.

CLN2 神经元蜡样脂褐质沉着症是一种罕见的隐性遗传性视网膜和神经退行性疾病，由编码可溶性溶酶体酶三肽基肽酶-1 (TPP1)的TPP1中的有害序列变异引起。患有这种疾病的儿童发育正常，但在 2-4 岁时开始出现神经系统体征和视觉缺陷。进展为失明的视力丧失与进行性视网膜变性和视网膜功能损害有关。在具有TPP1的狗 CLN2 疾病模型中发生了类似的视网膜功能逐渐丧失和视网膜变性空序列变体。使用狗模型进行了研究，以确定在视网膜功能障碍发作后开始玻璃体内注射重组人 TPP1 (rhTPP1) 是否可以减缓或阻止视网膜功能衰退和退化的进展。TPP1 -空狗在 23.5-25 周龄时开始在一只眼睛和另一只眼睛玻璃体内注射 rhTPP1，然后在 34-40 周时对 4 只狗中的 3 只进行第二次注射。定期重复眼科检查、体内眼部成像和视网膜电图 (ERG) 以监测视网膜结构和功能。当这些狗在终末期神经系统疾病（40-45 周龄）被安乐死时，对从这些狗收集的眼睛进行视网膜组织学评估。玻璃体内注射 rhTPP1 在单次治疗后可有效保持视网膜功能（通过视网膜电图测量）和视网膜形态长达 4 个月。