Stem Cells for Replacing Damaged Retinal Cells


Stem cells are pluripotent, meaning that they are capable of differentiating into a variety of cells types. They exist as embryonic stem (ES) cells or as induced pluripotent stem (iPS) cells. The later are produced from mature cells. Stem cell therapy is being studied as a means for replacing damaged retinal cells. In fact, it was recently demonstrated that adult somatic (e.g., skin) cells can be persuaded (in vitro) to form stem cells that are capable of becoming cells of the eye. This remarkable finding raises the possibility of generating new tissue from mature cells of people who have retinal disease to serve as pluripotent cells that could be grafted into the eyes to take on characteristics of normal vision cells. Every year at the ARVO annual meeting certain topics generate a buzz. Stem cell research and stem cell-based treatments received a lot of attention this year.


Several laboratories have developed protocols for forming retinal cells from ES and iPS cells and have shown that, in animals with retinal degenerative disease, retinal cells derived from both can become part of the retina.


In the U.S., stem cell-based products intended for patient administration are regulated by the FDA Center for Biologics Evaluation and Research. The FDA considers factors such as the viability of the stem cells transplant, migration of cells from the site of delivery, further differentiation and proliferation of the stem cells to other phenotypes and possible tumorgenicity, and functional physiologic integration of the cells. Stem cell research is young and, before being applied to humans, needs to be studied thoroughly for safety and therapeutic efficacy.

(T.A. Reh; K. Wallace, D.O. Clegg, M. Friedlander, D.W. Fink)

EYS Mutations in RP Patients in France

Scientists studying RP in French patients believe that mutations in the EYS gene are a major cause of retinitis pigmentosa (RP) in France and probably elsewhere. The EYS gene is the largest known gene in the human eye, spanning over two megabits. The researchers found 37 likely mutations in the EYS gene among more than 200 people with sporadic or autosomal recessive retinitis pigmentosa for whom known mutations had previously been ruled out. Some patients had a single mutation while others had several. Most patients had classical signs of RP and a typical course of relatively preserved central vision until late in the disorder. This prevalence of EYS gene mutations in this population suggests a prominent role in other cases of RP.

(I.S. Audo, J.-A. Sahel, S. Mohand-Saïd, M.-E. Lancelot, I. Barragan, M.M. Abd El-Aziz, E.F. Nandrot, G. Antinolo, S.S. Bhattacharya, C. Zeitz)

(Other researchers recently reported a high prevalence of EYS mutations in Israeli and Palestinian families who have autosomal recessive RP.  The researchers are D. Bandah-Rozenfeld, K.W. Littink, T. Ben-Yosef, T.M. Strom, I. Chowers, R.W. Collin, A.I. den Hollander, I. van den Born, M.N. Zonneveld, S. Merin, E. Banin, F.P. Cremers, and D. Sharon. Their report was published online ahead of print April 7, 2010; IOVS. doi:10.1167/iovs.09-4732.)

Adeno-associated Virus (AAV)-Mediated RPE65 Gene Replacement Trials in Humans with LCA


In humans, mutations in RPE65 can lead to Leber’s congenital amaurosis or retinitis pigmentosa.  In young adults with RPE65-associated Leber’s congenital amaurosis, subretinal injection of a RPE65 transgene has been shown to improve vision and retinal function. A new Phase 1 dose-escalation study of patients ranging in age from 8 to 44 shows the greatest improvements in the younger subjects.


(E.A. Pierce)

Inhibition of the Retinal Vasculature Endothelial Cell Tight Junctions to Provide Systemic Neuroprotective


Endothelial cells of the retinal microvasculature are bound to adjacent cells by “tight junctions” that prevent passage of potentially harmful substances from the blood into surrounding tissues. Unfortunately, this inner blood-retina barrier (IBRB) also thwarts transfer of potentially therapeutic drugs. Researchers report that they have been able to breach the endothelial barrier and administer drug therapy, in preclinical models, by systemic administration of siRNA against claudin-5, a protein in the tight junctions, or by locally incorporating shRNA targeting claudin-5 into an inducible AAV-2/9 gene therapy vector system. (siRNAs and shRNAs disrupt gene expression.) The approaches have been effective in several animal models including the IMPDH1-/- mouse, a model of autosomal recessive retinitis pigmentosa.


(P. Humphries)