Topographic correlation between macular superficial microvessel density and ganglion cell-inner plexiform layer thickness in glaucoma-suspect and early normal-tension glaucoma
Abstract:Background/AimsTo investigate the topographic relationship between macular superficial microvessel density (SMD) and macular ganglion cell-inner plexiform layer (GCIPL) thickness in eyes with glaucoma-suspect (GS) and early normal-tension glaucoma (NTG).MethodsA total of 86 eyes of 86 patients with early NTG (standard automated perimetry mean deviation >−5.5 decibels) and a total of 25 eyes of 25 patients with GS were retrospectively reviewed. All of the subjects underwent optical coherence tomography (OCT)… Show more
“…1H). The NFL is comprised of axons of RGCs, and the altered thickness is consistent with earlier reports of RGC susceptibility to Hhcy [13,15,30,41,42]. Measurements of the NFL were within normal limits for PBS-injected eyes.Fig.…”
Hyperhomocysteinemia (Hhcy), or increased levels of the excitatory amino acid homocysteine (Hcy), is implicated in glaucoma, a disease characterized by increased oxidative stress and loss of retinal ganglion cells (RGCs). Whether Hhcy is causative or merely a biomarker for RGC loss in glaucoma is unknown. Here we analyzed the role of NRF2, a master regulator of the antioxidant response, in Hhcy-induced RGC death
in vivo
and
in vitro
. By crossing
Nrf2
−/−
mice and two mouse models of chronic Hhcy (
Cbs
+/-
and
Mthfr
+/-
mice), we generated
Cbs
+/-
Nrf2
−/−
and
Mthfr
+/-
Nrf2
−/−
mice and performed systematic analysis of retinal architecture and visual acuity followed by assessment of retinal morphometry and gliosis. We observed significant reduction of inner retinal layer thickness and reduced visual acuity in Hhcy mice lacking NRF2. These functional deficits were accompanied by fewer RGCs and increased gliosis. Given the key role of Müller glial cells in maintaining RGCs, we established an ex-vivo indirect co-culture system using primary RGCs and Müller cells. Hhcy-exposure decreased RGC viability, which was abrogated when cells were indirectly cultured with wildtype (WT) Müller cells, but not with
Nrf2
−/−
Müller cells. Exposure of WT Müller cells to Hhcy yielded a robust mitochondrial and glycolytic response, which was not observed in
Nrf2
−/−
Müller cells. Taken together, the
in vivo
and
in vitro
data suggest that deleterious effects of Hhcy on RGCs are likely dependent upon the health of retinal glial cells and the availability of an intact retinal antioxidant response mechanism.
“…1H). The NFL is comprised of axons of RGCs, and the altered thickness is consistent with earlier reports of RGC susceptibility to Hhcy [13,15,30,41,42]. Measurements of the NFL were within normal limits for PBS-injected eyes.Fig.…”
Hyperhomocysteinemia (Hhcy), or increased levels of the excitatory amino acid homocysteine (Hcy), is implicated in glaucoma, a disease characterized by increased oxidative stress and loss of retinal ganglion cells (RGCs). Whether Hhcy is causative or merely a biomarker for RGC loss in glaucoma is unknown. Here we analyzed the role of NRF2, a master regulator of the antioxidant response, in Hhcy-induced RGC death
in vivo
and
in vitro
. By crossing
Nrf2
−/−
mice and two mouse models of chronic Hhcy (
Cbs
+/-
and
Mthfr
+/-
mice), we generated
Cbs
+/-
Nrf2
−/−
and
Mthfr
+/-
Nrf2
−/−
mice and performed systematic analysis of retinal architecture and visual acuity followed by assessment of retinal morphometry and gliosis. We observed significant reduction of inner retinal layer thickness and reduced visual acuity in Hhcy mice lacking NRF2. These functional deficits were accompanied by fewer RGCs and increased gliosis. Given the key role of Müller glial cells in maintaining RGCs, we established an ex-vivo indirect co-culture system using primary RGCs and Müller cells. Hhcy-exposure decreased RGC viability, which was abrogated when cells were indirectly cultured with wildtype (WT) Müller cells, but not with
Nrf2
−/−
Müller cells. Exposure of WT Müller cells to Hhcy yielded a robust mitochondrial and glycolytic response, which was not observed in
Nrf2
−/−
Müller cells. Taken together, the
in vivo
and
in vitro
data suggest that deleterious effects of Hhcy on RGCs are likely dependent upon the health of retinal glial cells and the availability of an intact retinal antioxidant response mechanism.
“…Within the perimetrically undamaged area, RNFL was significantly lower in the superior nasal and upper nasal sectors (P=0.02) but VD showed no changes 11 . For NTG, a change in vascular density in the peripapillary region was registered [12][13][14][15][16][17] .…”
Background. Hypertensive glaucoma (HTG) causes damage to the retinal ganglion cells and eventually to the entire visual pathway due to high intraocular pressure (IOP). However, increased IOP will also affect the vessel density (VD) of the posterior pole of the eye and the related retinal ganglion nerve fibres (RNFL). In normotensive glaucoma (NTG), the retinal ganglion cells are relatively intact. The pathology is at the level of ganglion fibres. The unanswered question is what has altered ganglion cell fibres at the level of the retina and optic nerve head in NTG? Aim. The aim of this study was to determine whether there is a correlation between the retinal nerve fibre layer (RNFL) and vessel density (VD) at the same altitudinal half of the retina and the sum of sensitivities of the contralateral half of the visual field of the same eye in hypertensive and normotensive glaucoma (NTG). Methods. Our group included 20 patients with HTG and 20 patients with NTG. The Pearson's correlation coefficient r was used for evaluation of the relationship of the peripapillary RNFL and VD, visual field (using the fast threshold glaucoma program) as the sum of sensitivities in apostilbs (asb) to the extent of 0-22 degrees. The results of sensitivity were compared with the RNFL and VD of the contralateral altitudinal half of the retina in the same eye. Results. In the HTG group there was a moderate relationship between RNFL and VD (both hemifields), but no relationship between RNFL and VF. VD SH and VF IH showed weak correlation and VD IH and VF SH showed no correlation. In patients with NTG, we found a strong correlation between RNFL and VD (both hemifields), between VD SH and VF IH a moderate correlation, between VD IH and VF SH also a moderate correlation and a weak correlation between RNFL and VF. Conclusion. By comparing the RNFL and VD at the same altitudinal halves of the retina, we found a moderate correlation in HTG and a strong correlation in NTG. We found no or a weak correlation between VD and VF in HTG. In NTG the relationship between VD and VF showed a strong correlation. These findings reveal the differences in the diagnostic groups.
“…More recently, macular microvasculature was also investigated in glaucoma, and several studies reported significantly decreased SCP vessel density, with relative sparing of the DCP [ 121 , 122 , 123 , 124 ]. The SVC has been found to supply blood to the nerve fiber layer and ganglion cell layer.…”
Retinal microcirculation shares similar features with cerebral small blood vessels. Thus, the retina may be considered an accessible ‘window’ to detect the microvascular damage occurring in the setting of neurodegenerative disorders. Optical coherence tomography angiography (OCT-A) is a non-invasive imaging modality providing depth resolved images of blood flow in the retina, choroid, and optic nerve. In this review, we summarize the current literature on the application of OCT-A in glaucoma and central nervous system conditions such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Future directions aiming at evaluating whether OCT-A can be an additional biomarker for the early diagnosis and monitoring of neurodegenerative disorders are also discussed.
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