Functional rescue of experimental ischemic optic neuropathy with αB-crystallin.

Abstract

PURPOSE:

Anterior ischemic optic neuropathy (AION) is an important cause of acute vision loss in adults, and there is no effective treatment. We studied early changes following experimental AION and tested the benefit of a potential treatment.

MATERIALS AND METHODS:

We induced experimental AION in adult mice and tested the effects of short-term (daily for 3 days) and long-term (every other day for 3 weeks) αB-crystallin (αBC) treatment using histological and serial intracranial flash visual evoked potential recordings.

RESULTS:

One day after experimental AION, there was swelling at the optic nerve (ON) head and increased expression of αBC, a small heat shock protein important in ischemia and inflammation. This upregulation coincided with microglial and astrocytic activation. Our hypothesis was that αBC may be part of the endogenous protective mechanism against injury, thus we tested the effects of αBC on experimental AION. Daily intraveneous or intravitreal αBC injections did not improve visual evoked potential amplitude or latency at days 1-2. However, αBC treatment decreased swelling and dampened the microglial and astrocytic activation on day 3. Longer treatment with intravenous αBC led to acceleration of visual evoked potential latency over 3 weeks, without improving amplitude. This latency acceleration did not correlate with increased retinal ganglion cell survival but did correlate with complete rescue of the ON oligodendrocytes, which are important for myelination.

CONCLUSIONS:

We identified αBC as an early marker following experimental AION. Treatment with αBC enhanced this endogenous, post-ischemic response by decreasing microglial activation and promoting ON oligodendrocyte survival.

• Authors: S Pangratz-Fuehrer, K Kaur, S S Ousman, L Steinman, Y J Liao
• Journal: Eye (London, England) (Eye (Lond)) Vol. 25 Issue 6 Pg. 809-17 (Jun 2011) ISSN: 1476-5454 [Electronic] England
• PMID: 21475310 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Heat-Shock Proteins
• alpha-Crystallin B Chain

Topics

• Animals
• Cell Survival (drug effects)
• Disease Models, Animal
• Evoked Potentials, Visual (drug effects)
• Heat-Shock Proteins (metabolism, therapeutic use)
• Injections, Intravenous
• Intravitreal Injections
• Mice
• Oligodendroglia (cytology)
• Optic Disk (pathology)
• Optic Neuropathy, Ischemic (drug therapy, metabolism)
• Retinal Ganglion Cells (cytology)
• Up-Regulation
• alpha-Crystallin B Chain (metabolism, therapeutic use)