16 / 16
Page 82
allied
academies
Ophthalmol Case Rep 2017 Volume 1 Issue 1
August 21-23, 2017 | Toronto, Canada
EYE AND VISION
3
rd
International Conference on
Statement of theproblem:
Age relatedmacular degeneration
(AMD) is the major cause of blindness with huge financial
and social impact. Unfortunately, treatment is still very
limited. Advance in stem cell biology offers real promise
to save vision. Current stem cell-based therapies in clinical
trials to treat AMD aim to replace retinal pigment epithelium
(RPE). However, reported efficacies have been inconsistent,
often poor, and the mechanisms of retinal protection remain
poorly defined. RPE replacement strategy is complexed by
several factors. Grafting early on is prohibited by diseased
RPE cells still occupying Bruch’s membrane (BM), whereas
the problemwith grafting too late is that insufficient numbers
of functional photoreceptors remain. The co-dependency
between RPE and photoreceptors leaves a narrow window of
time in which interventions have the best chance of success.
Another important consideration for RPE cell grafts is that
BM undergoes progressive degeneration in AMD. Studies
have clearly demonstrated that healthy RPE fails to resurface
BM in both animal experiments and clinical trials.
An alternative cell type that does not require attachment to
BM, preserves vision, and reduces the burden of aging RPE
cells may be a viable option for treating AMD.
Methodology & Theoretical Orientation:
Clinical grade
NPCs were injected into the sub retinal space of rodent
model for retinal degeneration to validate its efficacy and
large animal model-Yucatan mini pig to test the feasibility of
delivering viable NPCs. At several time points, visual function
was examined by electro retinography (ERG and optokinetic
response (OKR); retinal lamination and graft distribution
was evaluated by spectral domain optimal coherence
tomography (SD-OCT). Histological correlation with visual
function was performed.
Findings:
NPCs survived for long term, migrated extensively
in the sub retinal space and offered dramatic preservation
of photoreceptors. NPCs preserved RPE cell integrity, self-
assembled as a layer in graft-secreted extracellular matrix
(ECM) that did not require attachment to BM while offering
vision preservation. NPCs reduced the burden of RPE cells by
phagocytizing and degrading
Photoreceptor outer segments. NPCs were successfully
delivered to the sub retinal space of Yucatan mini pig in
the setting similar to human clinic; visual function was not
affected by sub retinal injection of NPCs as measured by ERG.
Retinal detachment due to the initial sub retinal injection
was quickly reattached as revealed by SD-OCT.
Conclusion & Significance:
As an alternative cell type to
RPE cells, NPCs offer dramatic photoreceptor and vision
preservation without needing to the attachment to the BM.
NPCs survive for long term and migrate extensively from
injection site. NPCs can be successfully delivered to large
animal model without affecting retinal function. NPCs hold
real potential for preserving existing retinal anatomy and
function.
e:
Shaomei.Wang@cshs.orgIND enabling study of transplanting clinical grade neural progenitor cells for the treatment of retinal
degeneration
Shaomei Wang
Los Angeles, CA