Retinal repair by stem cells

Stem cells repopulate the laser injured retina in mouse



Stem cell based therapies may provide treatment avenues for various degenerative disorders of retina and nervous tissue. The neurogenic potential of various types of stem cells has been tested and demonstrated by numerous workers in culture conditions as well as in various disease and injury models of retina and brain. However, side to side comparative analysis has not been carried out about the optimal route of administration for the stem cells. The present study was designed with an objective of investigating the comparative recruitment of Lin-ve BMSCs at the site of laser injury in mouse retina when delivered through intravenous and intravitreal routes.

The laser injury model of mouse retina provides a unique platform to induce optimal injury at RPE-photoreceptor junction. We purified Lin-ve BMSCs from mouse bone marrow by using MACS and then characterized these by FACS for Sca-1+ve stem cells. Enriched Lin-ve BMSCs were labeled with CFDA dye and transplanted through intravenous and intravitreal routes and their homing capacity was compared at various time points. The effect of varying the dose of transplanted cells (50,000, 100,000 and 150,000 cells) on homing capacity was also investigated. Lin-ve BMSCs showed incorporation into various layers of laser injured retina by both intravitreal and intravenous routes. However, the BMSCs transplanted through intravenous route showed migration to the injury site as early as 4 days in comparison to intravitreal route. A dose of 50,000 transplanted cells resulted in better incorporation and survival when compared to 150,000 cells. Retinal injury attracts stem cell recruitment and facilitates interaction of donor cells with stem cell niche around the injury site. The laser injury mouse model is a reproducible preclinical screening tool lending credibility to validate biotherapeutics. The model provides unique information about the route and dose of administration of stem cells that should be optimized according to the nature of disease before any clinical transplantation is planned. We are planning to test additional drugs, including some derived from Antarctica corals and sponges, and stem cells from other sources for their efficacy.

Stem cells repopulate the laser injured retina in mouse.

Laser injury has been used extensively in various retinal degeneration models. We have used this model to create an animal model of Bruch’s rupture and subsequently the retinal pigment epithelium, which leads to vision impairment and finally vision loss. This model was evaluated through Electrophysiological and molecular check points. Two different sources of stem cells viz. lineage negative stem cells derived from human umbilical cord blood and neurospheres derived from human fetal pigmented ciliary epithelium, were compared for their efficacy in the reversal or therapy of the artificially induced vision loss.  The two different sources were transplanted in the closest vicinity of the injury created, through the high risk sub retinal injections. The transplantation of the stem cells were done under the neural retina, above the RPE, and were analyzed for their homing efficacy. We hope to analyse if there is any cell replacement potential of this model for photoreceptors and/or any paracrine effects of the transplanted stem cells. The model is available for collaborators to validate their discovery phase molecules.


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