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Published on: July 8, 2025
Exogenous modulation of intrinsic optic nerve neuroprotective activity
Sinisa D Grozdanic1, Tatjana Lazic, Markus H Kuehn
1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. sgrozdan@iastate.edu
Summary
Neurotrophic factors BDNF and GDNF promote optic nerve recovery after retinal ischemia. Continuous release of these growth factors significantly protects optic nerve function in this experimental model.
Area of Science:
- Ophthalmology
- Neuroscience
- Regenerative Medicine
Background:
- Investigating the molecular and functional changes in the retina and optic nerve following acute intraocular pressure (IOP) elevation.
- Establishing an experimental model of retinal ischemia induced by acute ocular hypertension in rats.
Purpose of the Study:
- To characterize the molecular and functional consequences of acute IOP elevation on the rat retina and optic nerve.
- To evaluate the therapeutic potential of sustained neurotrophic factor delivery for optic nerve protection.
Main Methods:
- Induction of retinal ischemia via acute IOP elevation (110 mmHg/60 minutes) in rats.
- Molecular characterization using microarray, qRT-PCR, and immunohistochemistry.
- Intravitreal delivery of PLGA microspheres containing BDNF, GDNF, or CNTF, or empty microspheres.
- Functional assessment through pupil light reflex (PLR) and electroretinograms (ERG) over 60 days.
Main Results:
- Significant intrinsic upregulation of CNTF observed 10 and 25 days post-ischemia.
- No significant changes in GDNF, BDNF, or their receptor expression levels.
- CNTF microsphere treatment showed no functional recovery compared to controls.
- GDNF and BDNF microsphere treatments resulted in significant PLR recovery.
Conclusions:
- Sustained release of BDNF and GDNF via microspheres demonstrates significant neuroprotective effects on optic nerve function.
- The study highlights the potential of targeted neurotrophic factor delivery for treating optic nerve damage in ischemic conditions.
