Research

At the Laboratory of Photobiology in the Department of Ophthalmology, Keio University School of Medicine, we are exploring how disruptions in oxygen homeostasis contribute to the onset and progression of retinal diseases. The retina is one of the most oxygen-demanding tissues in the body, and even subtle fluctuations in its microenvironmental oxygen levels are closely associated with the pathogenesis of intractable retinal disorders such as age-related macular degeneration, diabetic retinopathy, and glaucoma.
Our laboratory has revealed that hypoxia-inducible factors (HIFs)—transcription factors that regulate cellular responses to hypoxic stress—play pivotal roles in both the initiation and progression of these diseases. Through a multifaceted approach employing various disease models, we have systematically elucidated the involvement of HIFs in retinal pathology.
Specifically, we have utilized mouse models that recapitulate key clinical conditions: laser-induced choroidal neovascularization for age-related macular degeneration, oxygen-induced retinopathy for diabetic retinopathy and retinopathy of prematurity, and light-induced retinal damage for retinitis pigmentosa. In these models, we observed pathological overexpression of HIFs during disease development and demonstrated that pharmacologic or genetic inhibition of HIFs suppresses disease progression. Furthermore, studies using genetically engineered mouse models further support the pivotal role of HIFs in disease pathogenesis. Complementing these in vivo findings, mechanistic analyses using various retinal cell lines have allowed us to identify disease-specific HIF-regulated pathogenic factors.
Based on these findings, the Laboratory of Photobiology is actively pursuing translational research, aiming to establish novel therapeutic strategies for retinal diseases through the perspective of oxygen metabolism.

We are conducting basic research on visual restoration using "optogenetics" as a novel approach to treat visual impairments caused by retinal degenerative diseases.
Optogenetics involves introducing light-sensitive proteins into retinal neurons that no longer respond to light, thereby artificially enabling them to react to light stimuli. Even in the late stages of retinal degeneration, where the photoreceptors responsible for vision have been lost, many of the inner retinal neurons—such as bipolar cells and retinal ganglion cells—remain viable. By conferring light sensitivity to these surviving cells, it becomes possible to utilize the remaining neural circuits to deliver visual information to the brain once again.
Our laboratory is actively developing and characterizing a wide variety of light-sensitive proteins—including microbial, animal-derived, and chimeric types—by comparing their light sensitivity, response speed, and signal amplification properties to identify the most suitable molecules for visual restoration.
A particular focus has been placed on the development and functional analysis of the chimeric opsin “GHCR (Gloeobacter and human chimeric rhodopsin)” which demonstrates high sensitivity and rapid response even under low-light conditions. In mouse models, GHCR has been shown to improve visually guided behavior and offer neuroprotective effects, contributing to its successful translation into clinical application.
We are also exploring which retinal cells should be targeted for gene delivery to achieve more physiological and sensitive visual signal transmission. These studies include experiments targeting retinal ganglion cells, bipolar cells, and even amacrine cells.
By reconstructing the function of neural circuits using light, our laboratory aims to restore lost vision. Through continued foundational research, the Photobiology Laboratory is paving the way for the next generation of vision restoration therapies.

Myopia is a refractive abnormality resulting from excessive elongation of the eyeball along its anteroposterior axis (axial elongation). This acquired morphological change significantly increases the risk of vision-threatening conditions, including glaucoma, retinal detachment, and macular degeneration. Epidemiological data from our study revealed that about 95% of a junior high school students in Tokyo are myopic, highlighting the alarming global rise in myopia prevalence. As myopia is now recognized as a major risk factor for visual impairment, there is an urgent need to develop effective intervention strategies.
In our laboratory, we are dedicated to pioneering a new research field, "Myopia Biology," which seeks to develop effective intervention strategies for myopia by elucidating the molecular and cellular biological mechanisms underlying the acquired morphological changes in the eyeball associated with this condition. We are conducting the following research, focusing mainly on the posterior eye (retina, retinal pigment epithelium, choroid, sclera).

Realizing vision restoration requires not only innovative basic research but also effective translational efforts that bridge laboratory discoveries to clinical applications. Particularly in the field of gene therapy, significant hurdles exist, including the establishment of reliable visual function assessment methods and the validation of treatment efficacy through clinical trials.
At the Laboratory of Photobiology, Keio University, we are actively engaged in translational research efforts to advance vision restoration technologies into societal implementation. In collaboration with Restore Vision, a spin-off venture from our laboratory, we are establishing and validating clinical evaluation systems critical for successful translation.
For instance, we are collaboratively developing a comprehensive multi-dimensional visual assessment framework designed to accurately evaluate treatment outcomes in patients with ultra-low vision. This framework integrates retinal light sensitivity tests (Full-field Stimulus Testing; FST), behavioral tasks (such as Table Test and Door Task), and quality-of-life assessments (Impact of Vision Impairment – Very Low Vision; IVI-VLV). This approach is beginning to enable scientific detection of subtle visual changes that traditional visual acuity charts fail to capture.
Furthermore, our partnership with Restore Vision extends to conducting clinical trials to verify gene therapy products' safety and efficacy. Together, we address medical and technical aspects necessary for rigorous clinical evaluation. By systematically overcoming various challenges, from establishing robust evaluation methods to conducting clinical validations, we strive to make vision restoration therapies tangible.
By integrating fundamental molecular research with practical clinical applications, we aspire to provide new possibilities for individuals who have lost their vision. The Laboratory of Photobiology remains dedicated to advancing translational research, with a clear vision of translating our scientific achievements into practical medical benefits.