Markers of the sympathetic, parasympathetic and sensory nervous system are altered in the human diabetic choroid

Peptides. 2021 Dec:146:170661. doi: 10.1016/j.peptides.2021.170661. Epub 2021 Sep 24.

Abstract

Background: We sought to evaluate alterations in markers of the autonomic nervous system in human diabetic choroid.

Methods: Eighteen eyeballs from subjects with diabetes and 22 eyeballs from subjects without diabetes were evaluated in this study. Synaptophysin, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DβH), neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), vesicular monoamine transporter II (VMAT-2), vesicular acetylcholine transporter (VAChT), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) levels were detected by western blot analysis and immunofluorescence was performed in some cases. Furthermore, differences in adrenergic (α1- and β2-subtypes) and cholinergic (M1 and M3) receptor levels between diabetic subjects and controls were noted.

Results: Decreased synaptophysin levels were found in diabetic choroids by western blot analysis and a reduction of synaptophysin-immunoreactive nerves was also found by immunofluorescence. Furthermore, a decrease of the levels of the key enzyme (TH) and transporter (VMAT2) of norepinephrine was evident both by western blot analysis and immunofluorescence. Additionally, increased NPY, VAChT, nNOS, and CGRP levels were observed in diabetic choroids. The levels of adrenergic (β2 subtype) and acetylcholine (M1 subtype) receptors decreased in diabetic choroids, as shown by western blotting and although the differences in α1 and M3 were not significant, there was a downward trend.

Conclusions: In the diabetic choroid, the levels of neurotransmitters, enzymes, and receptors associated with choroidal blood flow regulation are altered. These changes may affect the regulation of choroidal blood flow and may be associated with impaired retinal function and retinal pathology.

Keywords: Acetylcholine; CGRP; Choroid; Diabetes retinopathy; Diabetic autonomic neuropathy; NPY; Norepinephrine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism
  • Calcitonin Gene-Related Peptide / metabolism
  • Case-Control Studies
  • Choroid / innervation*
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / physiopathology*
  • Humans
  • Male
  • Middle Aged
  • Neurons / metabolism
  • Neuropeptide Y / metabolism
  • Nitric Oxide Synthase Type I / metabolism
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Receptors, Adrenergic, beta-2 / metabolism
  • Receptors, Muscarinic / metabolism
  • Tyrosine 3-Monooxygenase / metabolism
  • Vesicular Acetylcholine Transport Proteins / metabolism
  • Vesicular Monoamine Transport Proteins / metabolism

Substances

  • Biomarkers
  • Neuropeptide Y
  • Receptors, Adrenergic, alpha-1
  • Receptors, Adrenergic, beta-2
  • Receptors, Muscarinic
  • SLC18A2 protein, human
  • Vesicular Acetylcholine Transport Proteins
  • Vesicular Monoamine Transport Proteins
  • Nitric Oxide Synthase Type I
  • Tyrosine 3-Monooxygenase
  • Calcitonin Gene-Related Peptide