Glaucoma, the leading cause of irreversible blindness, is a heterogeneous group of diseases characterized by progressive loss of retinal ganglion cells (RGCs) and their axons and leads to visual loss and blindness. Risk factors for the onset and progression of glaucoma include systemic and ocular factors such as older age, lower ocular perfusion pressure, and intraocular pressure (IOP). Early signs of RGC damage comprise impairment of axonal transport, downregulation of specific genes and metabolic changes. The brain is often cited to be the highest energy-demanding tissue of the human body. The retina is estimated to have equally high demands. RGCs are particularly active in metabolism and vulnerable to energy insufficiency. Understanding the energy metabolism of the inner retina, especially of the RGCs, is pivotal for understanding glaucoma’s pathophysiology. Here we review the key contributors to the high energy demands in the retina and the distinguishing features of energy metabolism of the inner retina. The major features of glaucoma include progressive cell death of retinal ganglions and optic nerve damage. Therefore, this review focuses on the energetic budget of the retinal ganglion cells, optic nerve and the relevant cells that surround them.

Glaucoma is a leading cause of irreversible blindness worldwide. While intraocular pressure (IOP) presents a major risk factor, the underlying pathophysiology still remains largely unclear. The correlation between vascular abnormalities and glaucoma has been deliberated for decades. Evidence for a role played by vascular factors in the pathogenesis of glaucomatous neurodegeneration has already been postulated. In addition, the fact that glaucoma causes both structural and functional changes to retinal blood vessels has been described. This review aims to investigate the published evidence concerning the relationship between vascular abnormalities and glaucoma, and to provide an overview of the “chicken or egg” dilemma in glaucoma. In this study, several biomarkers of glaucoma progression from a vascular perspective, including endothelin-1 (ET-1), nitric oxide, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs), were identified and subsequently assessed for their potential as pharmacological intervention targets.

Oxidative stress (OS) damage can cause significant injury to cells, which is related to the occurrence and development of many diseases. This pathological process is considered to be the first step to trigger the death of outer retinal neurons, which is related to the pathology of retinal degenerative diseases. Hydrogen sulfide (H₂S) has recently received widespread attention as a physiological signal molecule and gas neuromodulator and plays an important role in regulating OS in eyes. In this article, we reviewed the OS responses and regulatory mechanisms of H₂S and its donors as endogenous and exogenous regulators in retinal degenerative diseases. Understanding the relevant mechanisms will help to identify the therapeutic potential of H₂S in retinal degenerative diseases.

The roles of vascular dysfunction and chronic stress have been extensively discussed in the pathophysiology of glaucoma. Our aim was to test whether chronic stress causes retinal vascular dysfunction and therewith induces retinal ganglion cells (RGCs) loss. Twelve mice underwent chronic social defeat (CSD) stress, while 12 mice received control treatment only. Intraocular pressure (IOP) was measured with a rebound tonometer. Blood plasma corticosterone concentration and adrenal gland weight were used to assess stress levels. Brn-3a staining in retinas and PPD staining in optic nerve cross sections were conducted to assess the survival of RGCs and axons respectively. The ET-1 and α-SMA levels were determined in retina. Retinal vascular autoregulation, functional response to various vasoactive agents and vascular mechanics were measured using video microscopy. No significant difference in IOP levels was observed during and after CSD between CSD mice and controls. CSD stress caused hypercortisolemia 2 days post-CSD. However, increased corticosterone levels went back to normal 8 months after CSD. CSD-exposed mice developed adrenal hyperplasia 3 days post-CSD, which was normalized by 8 months. RGC and axon survival were similar between CSD mice and controls. However, CSD stress caused irreversible, impaired autoregulation and vascular dysfunction of retinal arterioles in CSD mice. In addition, impaired maximal dilator capacity of retinal arterioles was observed 8 months post-CSD rather than 3 days post-CSD. Remarkably, ET-1 levels were increased 3 days post-CSD while α-SMA levels were decreased 8 months post-CSD. We found that CSD stress does not cause IOP elevation, nor loss of RGCs and their axons. However, it strikingly causes irreversible impaired autoregulation and endothelial function in murine retinal arterioles. In addition, CSD changed vascular mechanics on a long-term basis. Increased ET-1 levels and loss of pericytes in retina vessels may involve in this process.

Glaucoma is a group of diseases characterized by the progressive loss of retinal ganglion cells and their axons. Elevated intraocular pressure (IOP) is the main clinical manifestation of glaucoma. Despite being in the focus of the studies for decades, the characteristic and the exact pathology of neurodegeneration in glaucoma remains unclear. Oxidative stress is believed to be one of the main risk factors in neurodegeneration, especially its damage to the retinal ganglion cells. Hydrogen sulfide (H₂S), the recently recognized gas signaling molecule, plays a pivotal role in the nervous system, vascular system, and immune system. It has also shown properties in regulating oxidative stress through different pathways in vivo. In this review, we summarize the distribution and the properties of H₂S within the eye with an emphasis on its role in modulating oxidative stress in glaucoma.

Background: To evaluate the long-term efficacy and safety of modified canaloplasty versus trabeculectomy in open-angle glaucoma. Methods: In total, 210 subjects with open-angle glaucoma were included. 70 were treated with Mitomycin C-augmented modified canaloplasty with enhanced subconjunctival filtration and 140 with Mitomycin C-augmented trabeculectomy. Cases were matched 1:2 by sex and age. Results: In canaloplasty and trabeculectomy groups, 61.4% and 57.9% of participants were female. Mean age was 60.0 ± 13.9 and 63.0 ± 12.2 years, median follow-up time was 4.6 [IQR 4.3, 5.05] years and 5.8 [IQR 5.4, 6.3]. Strict success was achieved in 20.0% and 56.4%, complete success in 24.3% and 66.4%, and qualified success in 34.3% and 73.6% (each p < 0.001). Kaplan–Meier survival analysis showed a better survival probability for trabeculectomy than for canaloplasty (p < 0.001) and Cox regression analysis revealed an HR of 6.03 (95%-CI 3.66, 9.93, p < 0.001) after canaloplasty. Trabeculectomy showed superiority in terms of IOP decrease (9.2 ± 7.9 mmHg vs. 13.7 ± 10.4 mmHg, p = 0.002), use of AGM (50.0% vs. 10.7%, p < 0.001), and the number of revision surgeries (41.4% vs. 21.4%, p = 0.004). Occurrence of complications was similar in both groups (14.5% vs. 7.5%, p = 0.19). Conclusions: Trabeculectomy showed superiority in efficacy and equality in safety compared to modified canaloplasty.