Retinitis pigmentosa (RP) is a refractory disease for which an effective method of treatment has not been established thus far. It is one of the top causes of vision loss in Japan. Although recent advances in molecular genetic research have revealed a diverse range of genetic anomalies that may cause this disease, many aspects of how each causative gene results in photoreceptor cell death remain unclear and genetic diagnostic systems have not been completely developed. With the aim of overcoming RP, we have been engaged in translational research (TR) on "RP Pathophysiology Elucidation and Treatment Development." In this review, we present new findings obtained from this research and discuss possibilities of establishing future treatment methods.
1. Neuroprotective gene therapy for RP
One of the final pathophysiologies common to cases of RP caused by various gene anomalies is photoreceptor cell apoptosis. To control this apoptosis, we have been conducting research to develop clinical applications of neuroprotective gene therapy using an original viral vector carrying pigment epithelium-derived factor gene. A clinical study correspond to phase I (UMIN000010260) is already underway, and preparations are underway for an investigator-initiated clinical trial (Phase I/IIa) to firmly establish this approach as a next-generation standard treatment.
2. RP pathophysiology elucidation
RP typically involves rod cell death caused by a genetic anomaly, which subsequently results in cone cell death. We hypothesized that some type of shared pathophysiology (environmental factor) unrelated to the genetic anomaly is involved in this process. Basic research using animal models of RP and analyses of data and clinical samples from >600 patients have revealed that (chronic) inflammation, oxidative stress, and retino-choroidal circulatory disorders (ischemia) are important environmental factors. These factors have been found to advance the condition of RP while interacting with each other.
3. Night-vision aid device development
Night blindness is one symptom of RP along with decreased visual acuity and narrowing of the visual field that lowers the quality of life of patients with RP. Because night blindness is observed in the early stages of the disease, in many patients, it limits the night-time outings that can be made. Collaborative research between industry and academia has resulted in the development of a device that uses a wearable see-through display and a highly sensitive camera to aid night vision in patients with night blindness. We hope that this device will become commercially available in the near future.
4. Steps to make TR on RP a success
Issues related to TR on RP include (1) the absence of large-scale animal models of the disease,(2) lack of appropriate treatment evaluation criteria, and (3) heterogeneous nature of RP, etc. We investigated solutions for each of these issues based on the thinking that solving these issues could be the key to making TR on RP a success.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 122: 200-222, 2018.