What Is a Retinal Organoid and How Does It Work?

A retinal organoid is a three-dimensional model of a human retina grown in a laboratory. Often called a “retina in a dish,” this miniature structure is generated from stem cells and mimics the layered organization of the retina in the human eye. Scientists guide these cells to develop into the various cell types for sight, creating a functional tissue that can respond to light.

These lab-grown tissues provide researchers a window into human vision. They allow for the study of how the retina forms and functions, something not possible with living subjects. This makes them a tool for understanding the origins of eye diseases and exploring new treatments.

How Lab-Grown Retinas Are Made

The creation of a retinal organoid begins with pluripotent stem cells, which possess the ability to develop into any other type of cell in the body. Scientists use induced pluripotent stem cells (iPSCs), which can be generated from adult cells like skin or blood. This allows researchers to create retinal models from any individual, which is useful for studying genetic diseases.

To turn these stem cells into a retina, they are cultured in a controlled lab environment with specific biochemical signals and growth factors. This process mimics the natural developmental stages of an embryo’s eye, and the cells begin to self-organize into the distinct layers of a mature retina without external scaffolding.

This self-assembly results in a three-dimensional, cup-shaped structure containing the main types of retinal cells. These include light-sensing photoreceptor cells, known as rods and cones, and retinal ganglion cells, which transmit visual information to the brain. The entire process can take over 150 days.

Modeling Eye Diseases

A primary application for retinal organoids is modeling hereditary eye diseases. By generating iPSCs from a patient with a condition like retinitis pigmentosa, scientists can grow a “disease in a dish.” This personalized model contains the specific genetic mutation causing the patient’s vision loss, allowing for a close view of the disease process.

These organoids allow observation of how a disease unfolds at the cellular level from its earliest stages. Researchers can track the dysfunction and death of photoreceptor cells to understand the mechanisms that drive vision loss. This is impossible in living patients, where a disease is often detected only after significant damage has occurred. By comparing the development of healthy organoids to diseased ones, scientists can pinpoint where things go wrong and develop targeted therapies.

A Platform for Developing New Treatments

Retinal organoids serve as a platform for testing new therapies. A human-relevant model of a retinal disease allows scientists to screen potential treatments, like new drug compounds and gene therapy, with greater accuracy than animal models.

Researchers can apply thousands of different chemical compounds to diseased organoids to identify any that can slow or halt the degenerative process. This high-throughput screening method is more efficient than traditional testing in animal models, which often do not fully replicate human retinal diseases.

This “in a dish” testing accelerates the preclinical phase of drug development, allowing promising candidates to advance to clinical trials more quickly. For gene therapies, organoids allow scientists to test the safety and effectiveness of delivering a correct copy of a faulty gene to the right cells before testing in a patient.

The Potential for Vision Restoration

A significant goal for retinal organoid technology is its application in regenerative medicine. The aim is to replace cells that have been lost to retinal degeneration, an approach that could restore vision to individuals with significant sight loss.

The concept involves growing healthy retinal cells from organoids and transplanting them into a patient’s eye. For diseases where photoreceptor cells have died, a patch of new, functional photoreceptors grown in the lab could be surgically placed into the retina. These new cells could then integrate with the surviving retinal circuitry, re-establishing the eye’s ability to detect light.

This area of research is advancing, with clinical trials exploring the transplantation of specific retinal cell types derived from stem cells. Challenges remain, such as ensuring the transplanted cells properly connect and function. Growing entire sheets of retinal tissue for transplantation is a long-term objective that could one day offer a cure for certain forms of blindness.

Scientific Hurdles and Ethical Considerations

Several scientific hurdles remain before retinal organoids can be used for widespread transplantation. A primary challenge is that lab-grown organoids do not achieve full maturity and resemble a fetal retina more than an adult one. They also lack a dedicated blood supply, or vasculature, which is needed to nourish the cells long-term after transplantation. The organoids are not connected to an optic nerve, limiting the ability to study their integration with the brain.

The use of stem cells has prompted ethical discussions, though the use of iPSCs has mitigated some concerns related to embryonic cells. As the technology advances toward creating tissues for transplantation, new considerations arise regarding the long-term implications of implanting lab-grown human tissue. These discussions help ensure the responsible development of this technology.