Growing Retinas in the Lab

It’s not easy to study the retina and its diseases—in particular macular degeneration, the leading cause of irreversible vision loss in people over 60. The retina’s macula, a small spot in the center of the retina where vision is the sharpest, is crucial for both central vision and visual acuity. It is also rich in cones, the photoreceptors that enable color vision. But the macula is unique to primates, and non-human primates are extremely costly to study.

Wei Liu, Ph.D.
Wei Liu, Ph.D.

Now, in research published online on May 9 in the Proceedings of the National Academy of Sciences of the United States of America, Einstein scientists have for the first time successfully produced cone-rich retinal organoids that resemble the human macula. The research is led by Wei Liu, Ph.D., assistant professor of ophthalmology and visual sciences and of genetics at Einstein.

Organoids—tiny clumps of cells grown in tissue culture, and resembling human tissues or organs—have emerged as powerful models for studying human development and disease. They are derived from stem cells—in this case, human embryonic stem cells, which Dr. Liu and his colleagues coaxed to develop into retinal organoids.

A three-dimensional movie constructed with multiphoton images show the outer segments of cone (green) and rod (red) photoreceptor cells in a 215-day retinal organoid.
Reproduced with permission from PNAS USA

The researchers showed that their organoids mimic the human macula in numerous cellular and molecular respects. For example, multiphoton microscopy revealed that the organoids’ cone photoreceptor cells were more abundant than their rod photoreceptors: the ratio of cones to rods in the organoids was as high as 2.8:1, reminiscent of the ratio of cones to rods in the human macula. In addition, single-cell RNA sequencing showed that the organoids’ rods and cones resembled human macula rods and cones with respect to the genes they expressed.

Cone-rich retinal organoids could be valuable resources for studying the biology of the human retina and may help reveal the molecular glitches that affect the retina, thereby aiding the search for treatments for macular degeneration and other blinding retinal diseases.