THE INFLUENCE OF A BENZODIAZEPINE RECEPTOR AGONIST ON THE STATE OF GLIA IN THE DIABETIC RETINOPATHY
SV Ziablitzev1, DB Zhupan1, OO Dyadyk2
- Bogomolets National Medical University, Kyiv, Ukraine
- Shupyk National University Healthcare of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz69.06.033
Abstract
Diabetic retinopathy is a progressive tissue-specific neurovascular complication of diabetes with a multifactorial
pathogenesis, in which microvascular disorders are preceded
by damage to nerve elements. The latter begin with the early
involvement of glia, including astrocytes and Müller cells.
Taking into account the establishment of GABA-ergic deficiency, the use of modulators of the GABA-benzodiazepine
receptor complex, for example, Carbacetam, which has shown
satisfactory neuroprotective properties, seems promising.
Diabetes mellitus was modeled by a single administration of
streptozotocin (50 mg/kg; “Sigma-Aldrich”, China) to threemonth-old male Wistar rats. Already after 7 days, according
to immunohistochemical detection of glial fibrillary acidic
protein (GFAP), reactive gliosis of astrocytes of the inner
retina layers was detected, to which Müller cells joined from
the 14th day. The content of GFAP in retinal tissues increased
significantly. GFAP-positive cells were in close contact with
foci of pathological angiogenesis in the inner layers of the
retina and also took part in the formation of fibrous proliferates
in the outer layers. Detection of caspase-3 showed the activation of apoptosis in astrocytes and radial processes of Müller
cells in the inner plexiform layer. Carbacetam in combination
with insulin reduced the expression of GFAP and caspase-3 in
the retina and prevented the development of reactive gliosis,
angiogenesis, and the formation of fibrous proliferates, which
makes it a candidate for further studies in the treatment of
diabetic retinopathy.
Keywords:
carbacetam; immunohistochemistry; immunoblotting; glial fibrillary acidic protein (GFAP); reactive gliosis; caspase-3; streptozotocin
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