Abstract
BackgroundOcular hypertension is a major risk factor for glaucoma, a neurodegenerative disease characterized by an irreversible decrease in ganglion cells and their axons. Macroglial and microglial cells appear to play an important role in the pathogenic mechanisms of the disease. Here, we study the effects of laser-induced ocular hypertension (OHT) in the macroglia, microglia and retinal ganglion cells (RGCs) of eyes with OHT (OHT-eyes) and contralateral eyes two weeks after lasering.MethodsTwo groups of adult Swiss mice were used: age-matched control (naïve, n = 9); and lasered (n = 9). In the lasered animals, both OHT-eyes and contralateral eyes were analyzed. Retinal whole-mounts were immunostained with antibodies against glial fibrillary acid protein (GFAP), neurofilament of 200kD (NF-200), ionized calcium binding adaptor molecule (Iba-1) and major histocompatibility complex class II molecule (MHC-II). The GFAP-labeled retinal area (GFAP-RA), the intensity of GFAP immunoreaction (GFAP-IR), and the number of astrocytes and NF-200 + RGCs were quantified.ResultsIn comparison with naïve: i) astrocytes were more robust in contralateral eyes. In OHT-eyes, the astrocyte population was not homogeneous, given that astrocytes displaying only primary processes coexisted with astrocytes in which primary and secondary processes could be recognized, the former having less intense GFAP-IR (P < 0.001); ii) GFAP-RA was increased in contralateral (P <0.05) and decreased in OHT-eyes (P <0.001); iii) the mean intensity of GFAP-IR was higher in OHT-eyes (P < 0.01), and the percentage of the retinal area occupied by GFAP+ cells with higher intensity levels was increased in contralateral (P = 0.05) and in OHT-eyes (P < 0.01); iv) both in contralateral and in OHT-eyes, GFAP was upregulated in Müller cells and microglia was activated; v) MHC-II was upregulated on macroglia and microglia. In microglia, it was similarly expressed in contralateral and OHT-eyes. By contrast, in macroglia, MHC-II upregulation was observed mainly in astrocytes in contralateral eyes and in Müller cells in OHT-eyes; vi) NF-200+RGCs (degenerated cells) appeared in OHT-eyes with a trend for the GFAP-RA to decrease and for the NF-200+RGC number to increase from the center to the periphery (r = −0.45).ConclusionThe use of the contralateral eye as an internal control in experimental induction of unilateral IOP should be reconsidered. The gliotic behavior in contralateral eyes could be related to the immune response. The absence of NF-200+RGCs (sign of RGC degeneration) leads us to postulate that the MHC-II upregulation in contralateral eyes could favor neuroprotection.
Highlights
Ocular hypertension is a major risk factor for glaucoma, a neurodegenerative disease characterized by an irreversible decrease in ganglion cells and their axons
Age-matched control: In naïve mice the astrocytes formed a homogeneous plexus on the nerve-fiber-retinal ganglion cells (RGCs) layer of glial fibrillary acid protein (GFAP)+ cells regularly distributed throughout the retina from the disc (Figure 3A) to the periphery
When we considered only those retinal areas with the highest intensities of GFAP immunoreaction (GFAP-IR), we found that in contralateral eyes the mean percentage of the retinal area occupied by GFAP + cells with intensities above 3,000 was higher than in naïve eyes (2.0 ± 1.8 and 0.2 ± 0.3, respectively; P = 0.05; unpaired T test) but it did not differ from values for ocular hypertension (OHT)-eyes (5.6 ± 4.3) (Figure 2)
Summary
Ocular hypertension is a major risk factor for glaucoma, a neurodegenerative disease characterized by an irreversible decrease in ganglion cells and their axons. Ocular hypertension is a major risk factor for glaucoma, a neurodegenerative disease characterized by an irreversible decrease of ganglion cells and their axons, the functional impact of which leads to a visual-field loss [1,2,3,4,5,6,7]. In the glaucomatous optic neuropathy, glial cells from the retina and from the optic nerve show abnormal behavior This results in the expression of glial fibrillary acid protein (GFAP) in Müller glia and the appearance of reactive astrocytes, which are characterized by a change in their form and their GFAP expression [21]
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