Growth hormone treatment is neuroprotective and preserves retinal function after an optic nerve insult in male rats

Abstract

Purpose : Growth hormone (GH) has neuroprotective effects in different regions of the nervous system, but it has not been evaluated in the mammalian visual system. This study tested the hypothesis that GH administration can promote retinal neuroprotection in an optic nerve crush (ONC) model in male wistar rats.

Methods : We compressed the optic nerve for 10 seconds and administered subcutaneous injections of GH (0.5 μg/g every 12 hours) for 24 hours or 14 days after injury. We evaluated the effects of GH upon several markers by qPCR, western blot, immunohistochemistry and full-field electroretinogram (ERG) and assessed optic nerve integrity using CTB Alexa 488 anterograde tracer.

Results : GH promoted RGCs survival 14 days after ONC. The ONC+GH group had significantly more RGCs compared to the ONC group, assessed by Brn3a immunohistochemistry. Likewise, the ONC+GH group exhibited increased immunoreactivity to the anti-apoptotic protein Bcl-xL in the RGC layer, whereas in the whole retinas a reduced immunoreactivity of the gliosis marker GFAP was observed as compared to the ONC group. CTB axonal labeling and Gap43 immunohistochemistry showed some optic nerve regeneration and active anterograde transport, with a few labeled axons in the lesion site of the ONC+GH group, contrary to the ONC group. Additionally, 14 days after ONC GH downregulated the mRNA expression levels of GFAP and NGF while upregulated Gap43 in comparison with the ONC group. While 24 hours after the injury, GH treatment restored mRNA expression levels of CNTF, GDNF, Gap43, SNAP25, NRXN1, NLGN1, Glul and GLAST and downregulated the protein levels of proapoptotic proteins Bad and Bax while recovering the levels of Bcl-xL. Finally, the functional assessment by mesotopic ERG revealed that the ONC group had a reduced amplitude of the b-wave and delayed implicit time of the a-wave compared to the sham group at five light intensities tested, while the ONC+GH group had a reduced b-wave at only one intensity and an unchanged a-wave.

Conclusions : GH has neuroprotective effects in an ONC model in male wistar rats. GH promotes RGCs survival, reduces gliosis and increases active axonal transport, likely through the regulation of genes involved in neuroprotection, survival, and synaptogenesis. Furthermore, GH prevented functional impairment as shown by ERG, indicating its potential as a therapeutic option for neurodegenerative diseases.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.