From an inauspicious start several years ago, the use of stem cells (SCs) in the treatment of several ocular and retinal diseases has picked up steam over the past year. As shown in Table 1, there are now more than 12 companies and institutions involved in research and clinical trials using a variety of SC types in the treatment of a handful of degenerative problems found in the eye, including several trials involving humans.

What are Stem Cells?

Every organ and tissue in our bodies is made up of specialized cells that originally come from a pool of SCs in the very early embryo (ESCs). Throughout our lives we rely to a much more limited degree on rare deposits of SCs in certain areas of the body (adult SCs) to regenerate organs and tissues that are injured or lost, such as our skin, our hair, our blood, and the lining of our gut.

SCs are like a blank microchip that can be programmed to perform particular tasks. Under proper conditions, SCs develop or differentiate into specialized cells that carry out a specific function, such as in the skin, muscle, liver, or in the eye. Additionally, SCs can grow extensively without differentiating, giving rise to more stem cells. These 2 characteristics of pluripotency and self-renewal distinguish SCs from other cells in the body and give SCs their tremendous therapeutic promise for a wide range of degenerative diseases.

The 4 most commonly used and described classes of SCs are embryonic stem cells (embryonic ESCs, also known as human embryonic stem cells, hESCs), induced pluripotent stem cells (ipSCs), adult SCs, and human parthenogenetic stem cells (hpSCs).

Beside the ESCs and adult SCs already used by the body, 2 other classes of SCs are increasingly used in medical research, the ipSCs and hpSCs.

ESCs are derived from fertilized human eggs (oocytes) in the early stages of development. They are truly pluripotent, in principle enabling them to become any body tissue and thus providing their tremendous clinical potential. However, ESCs are associated with significant ethical, political, and religious controversy because a fertilized egg, under the right circumstances, has the potential to develop into a human being. Another major (albeit much less publicized) issue with ESCs is that, because they are essentially a transplant from 1 person (the fertilized egg) to another (the recipient patient), an allogeneic treatment, therapeutic cells and tissues derived from ESCs can be expected to provoke an immune response from the recipient and be rejected.

In contrast, ipSCs are adult and fully differentiated cells (eg, skin cells) that are chemically, physically, genetically, or otherwise driven back to earlier developmental stages. Although creation of such cells does not involve the use or destruction of a fertilized egg, it does require dramatic changes in gene expression that may have unknown biological impact and likely will be subject to substantial scrutiny by regulatory authorities before any approval for therapeutic use. Also, due to immune rejection, ipSCs have to be derived from the individual patient (autologous therapy) which significantly limits clinical use and adds time and cost that will be increasingly difficult to implement in cost-contained health care systems worldwide. Finally, ipSCs cannot be used for hereditary disease therapy because they bear the genetic defects of the donor-patient.

Adult SCs are rare cells found in various organs or tissues in a person that have a limited ability to differentiate into cells with specific functions. They are older and less powerful than other types of SCs. While these SCs do not require use or destruction of a fertilized egg or extensive manipulation of gene expression, they are rare and hard to identify and they generally proliferate poorly, thus making it hard to produce therapeutic amounts.

hpSCs are derived from activated human oocytes. Parthenogenesis is a form of asexual reproduction in some amphibians and plants but does not occur naturally in mammals, including humans. Scientists have discovered a process for chemical activation of human eggs, similar to what the sperm does in normal fertilization but without any involvement of sperm. Some companies claim that this process results in hpSCs that are as pluripotent and proliferative as ESCs, yet avoid the ethical, political, and religious controversy surrounding use or destruction of human embryos with potential for viable human life. Furthermore, since there is no forced change of gene expression patterns, hpSCs are not likely to face the same safety and regulatory hurdle as ipSCs. Most important and unique relative to all other SC classes, hpSCs can be produced in a simplified immunogenetic (homozygous) form that enables each line to be an immune match for many millions of people.

Applications for Stem Cells in Ophthalmology

Cornea. Scarred and degenerative corneas represent 1 prime area of research for the use of SCs. Because of a lack of donated human eye bank corneas for transplantation, particularly in populous nations such as India and China and the emerging regions, the use of SCs to regenerate damaged corneal tissues could become highly valuable in those countries, where blindness due to damaged corneas is prevalent.

Glaucoma. There are only a few research programs using SCs for the middle areas of the eye, specifically in treating glaucoma. NeoStem has said it is working with Schepens Research Institute using the company's very small embryonic- like SCs (VSELs) in the treatment of glaucoma and agerelated macular degeneration (AMD), and Stemedica claims to be working with the Fyodorov Eye Institute in Moscow on a glaucoma program.

Lens. I know of no programs targeting the lens.

Retina/Macula/Vitreous. Most research efforts appear to be focused on the back of the eye, specifically retinal tissue and diseases. Areas of interest I have identified include regeneration of retinal epithelial cells for the treatment of both dry and wet forms of AMD; replacement of damaged photoreceptors; the growth of artificial retinas, again for treating AMD; and direct treatments for diseases such as retinitis pigmentosa, retinopathy of prematurity, diabetic retinopathy, Stargardt disease (Stargardt macular dystrophy), and retinal vein occlusion.

Clinical Trial Status

Table 2 shows the various clinical trials under way in the United States, Europe, Japan, and China to treat a variety of primarily retinal conditions. It should be noted that Advanced Cell Technology's clinical trials for both Stargardt disease and for treating dry AMD, at several eye institutes in the United States and Europe, have shown positive results in human patients.1 At least 21 patients have received SC treatments to date: 4 for Stargardt disease, 3 for dry AMD, 10 for ocular surface repair, and 4 for corneal epithelial SC deficiency.


As stated by Stephen Rose, PhD, Chief Research Officer at The Foundation Fighting Blindness, in his Eye on the Cure blog recently, “Of course, it would be nice if all the parts of our bodies, including our retinas, came with extended warranties so you could just swap them out when they go bad. But now that I think about it, that's what stem cells might do for us someday.”2

rv Arons is a retired consultant to the ophthalmic industry who now writes a blog, Irv Arons' Journal, focused on new technologies, including stem cells and gene therapy, for treating retinal diseases. His blog can be found at He may be contacted at

  1. Schwartz SD, Hubschman JP, Heilwell G, et al. Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet. 2012;379(9817):713-720.
  2. Rose S. There's more than one way to correct a genetic defect. Eye on the Cure. April 11, 2012. Available at: http:// Accessed June 6, 2012.