It’s like someone is slowly turning down the dimmer switch on the world. That’s how many people with retinitis pigmentosa (RP) describe a disease that gradually steals sight by killing the retina’s light-sensing cells. For many, the disease begins subtly — difficulty adjusting to darkness, trouble navigating dim hallways, and a gradual loss of peripheral vision. Over time, patients experience the loss of central vision, affecting their ability to perceive details and colors.
Despite affecting over 1.5 million individuals worldwide, there are no standard treatments for patients with RP. This is partially due to its genetic complexity. Thousands of unique mutations have been identified across more than 90 genes, each capable of disrupting the health of photoreceptor cells.
For a very small subset of patients, a gene therapy known as Luxturna provides a targeted option. Approved in 2017, Luxturna replaces the faulty RPE65 (retinal pigment epithelium-specific 65 kDa protein) gene, restoring the function of photoreceptors and improving vision in eligible patients. However, its applicability is extremely limited, as it only addresses this specific genetic mutation. For the vast majority of patients, effective therapies that can slow, halt, or reverse vision loss remain out of reach.
However, recent advances in optogenetics are now providing a broader, mutation-independent approach that could benefit many more patients. On November 28, Zhongmou Therapeutics announced that the FDA had cleared its Investigational New Drug (IND) application for ZM-02, a mutation-agnostic optogenetic gene therapy for advanced RP. This followed encouraging early results from their MOON trial in China, where legally blind patients with advanced RP showed remarkable improvements after a single injection of ZM-02.
Turning surviving cells into light sensors
Optogenetics was originally developed two decades ago as a neuroscience research tool, using light and genetic engineering to control neural activity. The approach involves introducing light-sensitive proteins, called opsins, into neurons, which can then be selectively activated or silenced with pulses of visible light.
In the retina, where photoreceptors may die, but other neurons often remain intact, optogenetics presents an exciting possibility: What if scientists could teach the surviving cells to sense light directly?
While photoreceptors detect light, retinal ganglion and bipolar cells process these signals and transmit them to the brain. Zhongmou’s therapy essentially rewires this visual circuitry, giving these cells the ability to sense light themselves. The company uses an adeno-associated virus (AAV) gene therapy to deliver instructions for a light-sensitive protein called channelrhodopsin into retinal ganglion or bipolar cells. This “functionalizes” the surviving neurons, allowing them to respond to light even in the absence of functional photoreceptors. Rather than repairing the broken circuitry, the therapy reroutes signals around it.
Early optogenetic proteins required intense light and often acted too slowly for natural, fluid vision, but Zhongmou’s platform uses PsCatCh2.0, a next-generation optogenetic protein engineered for exceptional light sensitivity and rapid kinetics. Preclinical studies in RP mouse models showed the protein restored robust retinal signaling, reactivated the visual cortex, and even reinstated visually guided behavior with improved acuity and fast response times.
A life-changing therapy
Zhongmou translated its preclinical work into the MOON investigator-initiated trial in China. Twelve patients with advanced RP, spanning multiple genetic mutations, received a single dose of ZM-02 and showed clinically meaningful improvements in functional vision. Seven of the nine patients treated with the active therapy were able to navigate low-light environments more effectively, and some even regained the ability to perceive colors — a first for an optogenetic therapy in humans. The treatment was well-tolerated, with no serious adverse events attributed to ZM-02, highlighting both the safety and potential efficacy of the approach.
These gains were also durable, persisting through 52 weeks after a single intravitreal injection. For many participants, the improvement was life-changing. Several were able to resume everyday activities they had long abandoned, including cycling and navigating both familiar and unfamiliar environments independently.
“Advanced RP is a disease where gene-specific therapies typically fail due to near-complete photoreceptor loss,” Yin Shen, founder and CEO of Zhongmou, said in the press release. “ZM-02 directly addresses this unmet need by bypassing degenerated photoreceptors and reactivating residual inner retinal circuits. At ATC 2025, we presented compelling evidence of patients transitioning from complete blindness to functional vision, regaining navigation capability in daily environments, and even safely returning to activities such as cycling without using external devices. These data represent a foundational step toward redefining what is clinically possible in late-stage RP.”
Following these results, the FDA has cleared its IND application for the PRISM trial, a multinational, randomized, single-masked, placebo-controlled study of ZM-02. This authorization makes ZM-02 the first optogenetic gene therapy originating from China to receive US IND clearance, placing Zhongmou among a select group of global leaders advancing the next wave of optogenetic medicine.
Beyond ZM-02, Zhongmou is developing a broad pipeline of gene and optogenetic therapies aimed at treating a range of inherited and acquired retinal diseases. Their programs include ZM-01 for X-linked retinoschisis, ZM-08 for dry age-related macular degeneration, and additional AAV- and opsin-based therapies targeting other retinal conditions.
A new wave of mutation-agnostic therapies for retinal disease
While Zhongmou is the first Chinese optogenetic therapy to receive FDA clearance, it is far from the only company developing such treatments. A growing ecosystem of biotech firms is pursuing mutation-agnostic therapies for retinal degeneration, each with its own approach.
This year, Nanoscope Therapeutics submitted a Biologics License Application (BLA) to the FDA for its own optogenetic gene therapy, MCO-010, targeting severe vision loss due to RP. The therapy introduces a proprietary Multi-Characteristic Opsin (MCO), which enables robust activation of retinal cells, allowing visual signals to bypass degenerated photoreceptors and reach the brain.
In its Phase 2b RESTORE trial, seven of 18 patients treated with MCO-010 showed clinically significant improvements at week 52, rising to 10 of 18 patients by week 76. The subsequent EXTEND study confirmed durability of response over five years, with no serious adverse effects reported, demonstrating both safety and long-term efficacy. The same therapy is also being tested in Stargardt disease.
BlueRock Therapeutics is taking a different approach, using cell replacement rather than gene therapy. Its OpCT-001 program is the first clinical trial to test induced pluripotent stem cell (iPSC)-derived photoreceptor cells for inherited retinal disorders, including RP and cone-rod dystrophy. The CLARICO trial is a first-in-human, multisite, two-part study designed to evaluate safety, tolerability, and early efficacy in up to 54 adults. Phase 1 focuses on safety with a dose-escalation design, while Phase 2 will assess effects on visual function, functional vision, and anatomical engraftment. The first patient was treated in early July 2025, marking the official start of the CLARICO trial and the first-ever clinical administration of an iPSC-derived photoreceptor cell therapy.
Ocugen is also developing a gene-agnostic therapy for RP and received FDA clearance in 2024 to launch its Phase 3 liMeliGhT trial of OCU400. OCU400 is a one-time subretinal AAV therapy delivering a nuclear hormone receptor gene. The therapy is designed to regulate multiple retinal processes, including photoreceptor development, metabolism, phototransduction, inflammation, and cell survival, potentially benefiting patients regardless of their specific disease-causing mutation. The study will enroll about 150 participants at 15 US sites, with one arm focused on individuals with the RHO (Rhodopsin) gene mutation and another for those with any RP-related mutation.
Ocugen is also advancing two Phase 1/2 programs using similar modifier-gene strategies: OCU410 for geographic atrophy and OCU410ST for Stargardt disease.
For decades, people with RP have had little more than patience to guide them through their fading vision. Luxturna offered a glimpse of what gene therapy could achieve, but only for a small few. Now, a new generation of optogenetic, cell, and gene-based therapies is expanding that promise — moving the field from rare, mutation-specific fixes toward treatments that could reach far more patients.
