# TISSUE ENGINEERED CELL TRANSPLANTATION FOR GLAUCOMA AND OPTIC NEUROPATHIES

> **NIH NIH R01** · UNIVERSITY OF MISSOURI KANSAS CITY · 2020 · $387,500

## Abstract

PROJECT SUMMARY/ABSTRACT
 Here we propose to develop a bio-engineered scaffold for the inner retina capable of being used as
both a model for this tissue and as a tool for cell transplantation. The neural retina, like other parts of the
central nervous system (CNS), fails to regenerate following cell death associated with injury or diseases. To
overcome this lack of regenerative repair, in diseases of the photoreceptors, cell replacement therapies have
been attempted. In these studies, injected cells are able to migrate into the correct lamina of the retina, form
synapses and function in animal models.1, 2 But can such a technique be used with diseases of the retinal
ganglion cells (RGCs) whose axons must regrow through the inhibitory environment of the diseased optic
nerve? The recent discovery of molecular mechanisms that promote optic nerve and CNS axon regeneration,
such as PTEN/SOCS3 or KLF4 deletion,3-6 combined with our studies showing transplanted RGCs extend
processes locally and form synapses in the inner plexiform layer (IPL),7 suggest that a transplantation therapy
may yet be possible for RGCs. However, data thus far suggest that transplanted cells are largely unable to
direct their axons towards the optic nerve head, perhaps due to developmental changes in retinal guidance
molecules.8, 9 Recently, we have developed a biodegradable radial electrospun scaffold (rES) cell delivery
vehicle capable of directing RGC axons radially, matching the orientation of the retinal nerve fiber layer
(NFL).10 However the RGCs seeded on the rES grow in both directions rather than having their axon growth
polarized towards the center as it is in the native tissue. In addition, it is not known if the transplanted cells will
be capable of extending their dendrites off of the cell delivery vehicle to form synapses with the injured retina.
In this study, we will further develop our cell delivery scaffold, immobilizing neurotrophic factors found during
development to polarize axon growth towards the scaffold center and the optic nerve head once transplanted.
In addition, we will combine the rES with a hydrogel composed of ECM matrix components of the developing
IPL in order to stimulate the transplanted RGC dendrites extension to retinal explants. Using these explant
models, we will evaluate the transplanted cells for functional synaptic connections through staining and the
propagation of light responses. Finally, using cells modified for regrowth through an injured optic nerve, we will
investigate the ability of axons from transplanted cells to enter the optic nerve. These studies will lead to the
creation of a retinal cell delivery device with the correct patterning of the ganglion cell layer and a hydrogel
system optimized to stimulate the integration of the transplanted cells. Taken together, this proposal will be an
important step towards our long term goal of restoring vision to those suffering from glaucoma and other optic
neuropathies.

## Key facts

- **NIH application ID:** 9935080
- **Project number:** 5R01EY028946-03
- **Recipient organization:** UNIVERSITY OF MISSOURI KANSAS CITY
- **Principal Investigator:** KARL ERICH KADOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,500
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935080

## Citation

> US National Institutes of Health, RePORTER application 9935080, TISSUE ENGINEERED CELL TRANSPLANTATION FOR GLAUCOMA AND OPTIC NEUROPATHIES (5R01EY028946-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9935080. Licensed CC0.

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