학술논문

Optic Nerve Head Myelin-Related Protein, GFAP, and Iba1 Alterations in Non-Human Primates With Early to Moderate Experimental Glaucoma
Document Type
article
Source
Investigative Ophthalmology & Visual Science. 63(11)
Subject
Biomedical and Clinical Sciences
Ophthalmology and Optometry
Neurodegenerative
Eye Disease and Disorders of Vision
Neurosciences
Eye
Animals
2'
3'-Cyclic Nucleotide 3'-Phosphodiesterase
Calcium
Disease Models
Animal
Glaucoma
Glial Fibrillary Acidic Protein
Myelin Basic Protein
Myelin Sheath
Optic Disk
Primates
Calcium-Binding Proteins
Microfilament Proteins
immunohistochemistry
optic nerve head
lamina cribrosa
myelin
microglia
macrophages
monkey
experimental glaucoma
astrocytes
Biological Sciences
Medical and Health Sciences
Ophthalmology & Optometry
Ophthalmology and optometry
Language
Abstract
PurposeThe purpose of this study was to test if optic nerve head (ONH) myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), glial fibrillary acidic protein (GFAP), and ionized calcium binding adaptor molecule 1 (Iba1) proteins are altered in non-human primate (NHP) early/moderate experimental glaucoma (EG).MethodsFollowing paraformaldehyde perfusion, control and EG eye ONH tissues from four NHPs were paraffin embedded and serially (5 µm) vertically sectioned. Anti-MBP, CNPase, GFAP, Iba1, and nuclear dye-stained sections were imaged using sub-saturating light intensities. Whole-section images were segmented creating anatomically consistent laminar (L) and retrolaminar (RL) regions/sub-regions. EG versus control eye intensity/pixel-cluster density data within L and two RL regions (RL1 [1-250 µm]/RL2 [251-500 µm] from L) were compared using random effects models within the statistical program "R."ResultsEG eye retinal nerve fiber loss ranged from 0% to 20%. EG eyes' MBP and CNPase intensity were decreased within the RL1 (MBP = 31.4%, P < 0.001; CNPase =62.3%, P < 0.001) and RL2 (MBP = 19.6%, P < 0.001; CNPase = 56.1%, P = 0.0004) regions. EG eye GFAP intensity was decreased in the L (41.6%, P < 0.001) and RL regions (26.7% for RL1, and 28.4% for RL2, both P < 0.001). Iba1+ and NucBlue pixel-cluster density were increased in the laminar (28.2%, P = 0.03 and 16.6%, P = 0.008) and both RL regions (RL1 = 37.3%, P = 0.01 and 23.7%, P = 0.0002; RL2 = 53.7%, P = 0.002 and 33.2%, P < 0.001).ConclusionsRetrolaminar myelin disruption occurs early in NHP EG and may be accompanied by laminar and retrolaminar decreases in astrocyte process labeling and increases in microglial/ macrophage density. The mechanistic and therapeutic implications of these findings warrant further study.