The Small Heat Shock Protein α-Crystallin B Shows Neuroprotective Properties in a Glaucoma Animal Model

Abstract

Glaucoma is a neurodegenerative disease that leads to irreversible retinal ganglion cell (RGC) loss and is one of the main causes of blindness worldwide. The pathogenesis of glaucoma remains unclear, and novel approaches for neuroprotective treatments are urgently needed. Previous studies have revealed significant down-regulation of α-crystallin B as an initial reaction to elevated intraocular pressure (IOP), followed by a clear but delayed up-regulation, suggesting that this small heat-shock protein plays a pathophysiological role in the disease. This study analyzed the neuroprotective effect of α-crystallin B in an experimental animal model of glaucoma. Significant IOP elevation induced by episcleral vein cauterization resulted in a considerable impairment of the RGCs and the retinal nerve fiber layer. An intravitreal injection of α-crystallin B at the time of the IOP increase was able to rescue the RGCs, as measured in a functional photopic electroretinogram, retinal nerve fiber layer thickness, and RGC counts. Mass-spectrometry-based proteomics and antibody-microarray measurements indicated that a α-crystallin injection distinctly up-regulated all of the subclasses (α, β, and γ) of the crystallin protein family. The creation of an interactive protein network revealed clear correlations between individual proteins, which showed a regulatory shift resulting from the crystallin injection. The neuroprotective properties of α-crystallin B further demonstrate the potential importance of crystallin proteins in developing therapeutic options for glaucoma.

17β-Estradiol Delivered in Eye Drops: Evidence of Impact on Protein Networks and Associated Biological Processes in the Rat Retina through Quantitative Proteomics

“…On the other hand, a decrease of CRYAA has been associated with retinal dystrophy [52] and glaucomatous optic neuropathy [44]. However, intravitreal injection of CRYAB at the time of the intraocular pressure (IOP) increase rescued RGCs in a rat model of glaucoma [53]. The latter study also provided proteomic evidence that CRYAB injection upregulated all (α, β and γ) subclasses of crystallins in the retina, which induced the broad neuroprotective effects observed.…”

On the origin of proteins in human drusen: The meet, greet and stick hypothesis

“…Retinal crystallins are also up-regulated in a variety of other retinal pathologies, including diabetic retinopathy, ischemia, mechanical injury and uveitis. The α-crystallin family plays a crucial role in neuroprotection and inflammation (Fort and Lampi, 2011), while the β-and γ-crystallins are small proteins with a possible ganglion cell protective role in glaucoma (Anders et al, 2017) and a role in retinal tissue remodeling and repair (Thanos et al, 2014). Consequently, the presence of these proteins in drusen points to a local cellular origin.…”

Neuroprotective Effects of HSF1 in Retinal Ischemia-Reperfusion Injury

“…In contrast, overactive HSF1 is involved in cancer by promoting cancer cell adaptation and survival in stressful conditions 5. It has been found that HSPs, including Hsp70, α-crystallins, Hsp40, and Hsp110, were able to enhance the survival of retinal neurons in models of glaucoma,8,9 optic nerve crush,9 polyglutamine disease,9,10 autoimmune uveitis,11,12 and retinal detachment 13. Moreover, inhibition of Hsp90 has neuroprotective effects in inherited retinal degeneration and polyglutamine diseases at least partially mediated by HSF1 14,15.…”