Search Results (326)

Objective: To investigate the neuroprotective effects of a Rho-associated kinase (ROCK) inhibitor on retinal ganglion cells (RGCs) in vitro and in vivo. Methods: For in vivo studies, a unilateral optic nerve crush mouse model was established. Then, 100 mM Y-27632 (a ROCK inhibitor) or saline was applied to the experimental eyes once a day for 14 days. The effects of the ROCK inhibitor were evaluated by counting the surviving RGCs in the enucleated flat retina tissues and measuring the inner retinal thickness using optical coherence tomography (OCT), the amplitude of the electroretinogram (ERG), and the change in intraocular pressure (IOP). For the in vitro study, RGCs were isolated from five-day-old mice using a modified immunopanning method with magnetic beads. The isolated RGCs were incubated for 72 h with various concentrations of Y-27632, after which TUNEL assays were performed to determine the number of surviving RGCs. Results: Y-27632 has neuroprotective effects, as it significantly increased the number of surviving RGCs by approximately 6.3%. OCT and ERG data also revealed that Y-27632 induced neuroprotective effects in vivo; furthermore, Y-27632 reduced IOP by approximately 18.3%. The in vitro study revealed the dose-dependent neuroprotective effects of Y-27632, with the highest dose of Y-27632 (1000 nM) increasing the RGC survival rate after 72 h of incubation compared with that of the control. Conclusions: The ROCK inhibitor Y-27632 may exert some neuroprotective effects on RGCs when it is used as an eye drop through an IOP-independent mechanism. Full article

Non-arteritic anterior ischemic optic neuropathy (NAION) leads to retinal ganglion cell (RGC) loss and visual impairment, with no effective treatment. This study investigated the neuroprotective effect of 670 nm photobiomodulation (PBM) in a rat NAION model (rNAION). Wistar rats received 670 nm light exposure (10-min, 3000 lux) twice daily for 3 days after rAION injury, followed by 4 days of light treatment once a day. This study evaluated the neuroprotective effects of 670 nm light in an rNAION model. Rats received 670 nm light therapy (10 min/day, 3000 lux) for seven days post-injury. Treatment improved visual function (a 3.36-fold increase in FVEP amplitude), enhanced RGC survival (1.55-fold), and reduced apoptosis (a 15.86-fold reduction in TUNEL-positive cells). Inflammatory cytokines and ED1+ macrophage infiltration were significantly decreased. Oxidative stress was attenuated, with increased ATP, Nrf2, and PGC-1α levels and improved mitochondrial dynamics. These findings support 670 nm light as a potential therapy for NAION. Full article

Background/Objectives: The early detection of retinal ganglion cell (RGC) dysfunction is critical for timely intervention in glaucoma suspects (GSs). The combined structure–function index (CSFI), which uses visual field and optical coherence tomography (OCT) data to estimate RGC counts, may be of limited utility in GSs. This study evaluates whether steady-state pattern electroretinogram (ssPERG)-derived estimates better predict early structural changes in GSs. Methods: Fifty eyes from 25 glaucoma suspects underwent ssPERG and spectral-domain OCT. Estimated RGC counts (eRGCC) were calculated using three parameters: ssPERG-Magnitude (eRGCC_Mag), ssPERG-MagnitudeD (eRGCC_MagD), and CSFI (eRGCC_CSFI). Linear regression and multivariable models were used to assess each model’s ability to predict the average retinal nerve fiber layer thickness (AvRNFLT), average ganglion cell layer–inner plexiform layer thickness (AvGCL-IPLT), and rim area. Results: eRGCC_Mag and eRGCC_MagD were significantly correlated with eRGCC_CSFI. Both PERG-derived models outperformed eRGCC_CSFI in predicting AvRNFLT and AvGCL-IPLT, with eRGCC_MagD showing the strongest association with AvGCL-IPLT. Conversely, the rim area was best predicted by eRGCC_Mag and eRGCC_CSFI. These findings support a linear relationship between ssPERG parameters and early RGC structural changes, while the logarithmic nature of visual field loss may limit eRGCC_CSFI’s predictive accuracy in GSs. Conclusions: ssPERG-derived estimates, particularly eRGCC_MagD, better predict early structural changes in GSs than eRGCC_CSFI. eRGCC_MagD’s superior performance in predicting GCL-IPLT highlights its potential utility as an early biomarker of glaucomatous damage. ssPERG-based models offer a simpler and more sensitive tool for early glaucoma risk stratification, and may provide a clinical benchmark for tracking recoverable RGC dysfunction and treatment response. Full article

Background: An acute angle-closure attack (AAC) is an ocular emergency that results from a rapid increase in intraocular pressure (IOP). Sustained IOP elevation induces severe degeneration of retinal ganglion cells (RGCs) without treatment. Overactivated microglia, key participants in innate immune responses, have critical roles in the pathogenesis of IOP-induced RGC death, although precise mechanisms remain unclear. In the present study, we used a rat ex vivo acute glaucoma model to investigate the role of microglial signaling in RGC death and examined whether pharmacological depletion of microglia using a CSF-1R inhibitor, PLX5622, exerts neuroprotection against pressure-induced retinal injury. Methods: Ex vivo rat retinas were exposed to hydrostatic pressure (10 mmHg or 75 mmHg) for 24 h. Pressure-dependent changes in retinal microglia and RGCs were detected by immunofluorescence. Morphological changes in the retina and RGC apoptosis were examined using light microscopy and TUNEL staining, respectively. The expression of NLRP3, active caspase-1, pro IL-1β, and IL-1β were examined using Western blotting. Effects of PLX5622, an agent that depletes microglia, were examined in morphology, apoptosis, and protein expression assays, while TAK-242, a TLR4 inhibitor, was examined against protein expression. Results: Pressure loading at 75 mmHg markedly increased activated microglia and apoptotic RGCs in the isolated retinas. Western blotting revealed increases in expression of NLRP3, active caspase-1, pro IL-1β, and IL-1β at 75 mmHg compared to 10 mmHg. Inhibition of pressure-induced increases in NLRP3 by TAK-242 indicates that pressure elevation induces RGC death via activation of the TLR4–NLRP3 inflammasome cascade. PLX5622 depleted microglia at 75 mmHg and significantly decreased expression of NLRP3, active caspase-1, pro IL-1β, and IL-1β at 75 mmHg, resulting in preservation of RGCs. Conclusions: These results indicate that pressure elevation induces proliferation of inflammatory microglia and promotes IL-1β production via activation of the TLR4–NLRP3 inflammasome cascade, resulting in RGC death. Pharmacological depletion of microglia with PLX5622 could be a potential neuroprotective approach to preserve RGCs from inflammatory cytokines in AAC eyes. Full article

Background/Objectives: The aim of this study was to evaluate the associations between optical coherence tomography angiography (OCTA)-based retinal vessel diameter (RVD) measurements, with retinal ganglion cell (RGC) function assessed by means of steady-state pattern electroretinography (ssPERG) using ganglion cell layer-inner plexiform layer thickness (GCL-IPLT) measurements and with Humphrey field analyzer (HFA) global indices in glaucoma suspects (GSs). Methods: Thirty-one eyes (20 participants) underwent a comprehensive ophthalmologic examination, ssPERG measurements utilizing the PERGLA paradigm, HFA, optical coherence tomography (OCT), and OCTA. The OCTA scans were processed using ImageJ software, Version 1.53, allowing for measurement of the RVD. Multiple linear regression models were used. Results: After controlling for age, race, central corneal thickness (CCT), and spherical equivalent (SE), a linear regression analysis found that the RVD explained the 4.7% variance in magnitude (Mag) (p = 0.169), 9.2% variance in magnitudeD (MagD) (p = 0.021), and 16.9% variance in magnitudeD/magnitude (p = 0.009). After controlling for age, CCT, and signal strength (SS), a linear regression analysis found that the RVD was significantly associated with the GCL-IPLT measurements (average GCL-IPL, minimum GCL-IPL, superior, superonasal, inferior, and inferonasal sectors) (p ≤ 0.023). An identical regression analysis where the RVD was replaced with the PERG parameters showed a significant association between the MagD and almost all GCI-IPLT measurements. RVD measurements were significantly associated with HFA VFI 24-2 (p = 0.004), MD 24-2 (p < 0.001), and PSD 24-2 (p = 0.009). Conclusions: Decreased RVD measurements were significantly associated with RGC dysfunction, decreased GCL-IPLT, and all HFA global indices in the GSs. Full article

Dominant Optic Atrophy (DOA) is the most common inherited optic neuropathy and presents as gradual visual loss caused by the loss of retinal ganglion cells (RGCs). Over 60% of DOA cases are caused by pathogenic variants in the OPA1 gene, which encodes a mitochondrial GTPase essential in mitochondrial fusion. Currently, there are no treatments for DOA. Here, we tested the therapeutic potential of an approach to DOA using CRISPR activation (CRISPRa). Homology directed repair was used to introduce a common OPA1 pathogenic variant (c.2708_2711TTAGdel) into HEK293T cells as an in vitro model of DOA. Heterozygous c.2708_2711TTAGdel cells had reduced levels of OPA1 mRNA transcript, OPA1 protein, and mitochondrial network alterations. The effect of inactivated Cas9 fused to an activator (dCas9–VPR) was tested with a range of guide RNAs (gRNA) targeted to the promotor region of OPA1. gRNA3 and dCas9–VPR increased OPA1 expression at the RNA and protein level towards control levels. Importantly, the correct ratio of OPA1 isoform transcripts was maintained by CRISPRa. CRISPRa-treated cells showed an improvement in mitochondrial networks compared to untreated cells, indicating partial rescue of a disease-associated phenotype. Collectively, these data support the potential application of CRISPRa as a therapeutic intervention in DOA. Full article

Older age is a risk factor for glaucoma, in which progressive retinal ganglion cell (RGC) loss leads to visual field defects and irreversible visual impairment and even blindness. We recently identified the involvement of cellular senescence in RGC cell death post-optic nerve injury. Here we further aimed to delineate the profile of RGC survival in mice with aging, a physiological process with increasing cellular senescence. The numbers of senescent cells in the ganglion cell layer (GCL) significantly and progressively increased starting at 8 months of age. Yet, significant reduction of ganglion cell complex layer thickness began in the 10-month-old mice, and significant reduction in the number of RGCs began in the 12-month-old mice as compared to the 2-month-old mice. Meanwhile, pyroptosis and ferroptosis markers as well as cellular senescence-related cell cycle arrest proteins p15^Ink4b, p16^Ink4a, p21^Cip1, and p53 were significantly and progressively increased in GCL. In contrast, there were no significant changes in dendritic field, complexity, and branches with increasing ages. Comparing between the 2- and 16-month-old mouse retinas, the differentially expressed genes were involved in the pathways of neurodegeneration, innate immunity, and mitochondrial ATP synthesis. In summary, this study revealed the gradual increase in senescent cells as well as pyroptosis and ferroptosis with progressive RGC reduction in mice with aging. Cellular senescence and the related cell death pathways are potential targets for age-related RGC reduction. Full article

Multisensory integration is fundamental for coherent perception and interaction with the environment. While cortical mechanisms of multisensory convergence are well studied, emerging evidence implicates specialized retinal ganglion cells—particularly melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs)—in crossmodal processing. This review explores how hierarchical brain networks (e.g., superior colliculus, parietal cortex) and ipRGCs jointly shape perception and behavior, focusing on their convergence in multisensory plasticity. We highlight ipRGCs as gatekeepers of environmental light cues. Their anatomical projections to multisensory areas like the superior colliculus are well established, although direct evidence for their role in human audiovisual integration remains limited. Through melanopsin signaling and subcortical projections, they may modulate downstream multisensory processing, potentially enhancing the salience of crossmodal inputs. A key theme is the spatiotemporal synergy between melanopsin and melatonin: melanopsin encodes light, while melatonin fine-tunes ipRGC activity and synaptic plasticity, potentially creating time-sensitive rehabilitation windows. However, direct evidence linking ipRGCs to audiovisual rehabilitation remains limited, with their role primarily inferred from anatomical and functional studies. Future implementations should prioritize quantitative optical metrics (e.g., melanopic irradiance, spectral composition) to standardize light-based interventions and enhance reproducibility. Nonetheless, we propose a translational framework combining multisensory stimuli (e.g., audiovisual cues) with circadian-timed melatonin to enhance recovery in visual disorders like hemianopia and spatial neglect. By bridging retinal biology with systems neuroscience, this review redefines the retina’s role in multisensory processing and offers novel, mechanistically grounded strategies for neurorehabilitation. Full article

Background/Objectives: To evaluate the neuromodulative effects of oral intake of a fixed combination of citicoline 500 mg plus homotaurine 50 mg plus vitamin B3 54 mg plus pyrroloquinoline quinone (CIT/HOMO/B3/PPQ) or of citicoline 800 mg alone (CIT800) on retinal ganglion cell (RGC) function in glaucoma patients by pattern electroretinogram (PERG) and to investigate the effects on quality of life and visual function. Methods: Consecutive patients with primary open-angle glaucoma with controlled IOP (<18 mmHg) receiving prostaglandin analogues as monotherapy; with two reliable visual fields (Humphrey 24-2 SITA Standard) per year in the last 2 years; and an early to moderate visual field defect (MD < −12 dB) were randomized to: arm A. topical therapy + CIT/HOMO/B3/PPQ for 4 months, followed by 4 months of topical therapy + CIT800; and arm B. topical therapy + CIT800 for 4 months, then topical therapy + CIT/HOMO/B3/PPG for 4 months. Patients were examined at month 0, 4, and 8. Complete ocular examination, visual field test, PERG, and quality of life assessment (NEI-VFQ25) were performed at each visit. Results: Forty patients were selected and completed the study, and none developed or reported an adverse event. The overall mean age was 64.2 (±7.7) years, 27 were male. At the end of the intake period of both products, patients exhibited higher P50 and N95-wave amplitudes and shorter latencies compared to baseline. The crossover analysis found that PERG parameters were better when patients received the CIT/HOMO/B3/PQQ combination with a statistically significant shorter peak time of 1.24 ms (95% CI, 0.37 to 2.10; p = 0.006) in the central P50 wave, 1.32 ms (95% CI, 0.44 to 2.22; p = 0.004) in the inferior P50 wave, and 1.70 ms (95% CI, 0.09 to 3.31; p = 0.038) in the inferior N95 wave; and a statistically significant increase of 0.35 µV (95% CI, 0.10 to 0.60; p = 0.006) in the superior N95 amplitude. The crossover analysis did not reveal any significant differences between the intake of CIT800 and CIT/HOMO/B3/PQQ in terms of visual acuity or IOP. During the intake of CIT/HOMO/B3/PQQ, a significant improvement was observed in the total mean score (p = 0.004), in the general health scale (GH, p = 0.01), in the color vision scale (p = 0.006), and in the peripheral vision scale (p = 0.001). Conclusions: The present study has shown that the addition of CIT/HOMO/B3/PQQ in early glaucoma improves PERG parameters and quality of life, likely by slowing down RGC aging and enhancing mitochondrial function more significantly than citicoline 800 mg alone. Full article

Background: Glaucoma is a leading cause of irreversible visual loss worldwide, characterized by progressive retinal ganglion cell (RGC) degeneration and optic nerve damage. Current therapies mainly focus on lowering intraocular pressure (IOP), yet fail to address pressure-independent neurodegenerative mechanisms. Melatonin, an endogenously produced indoleamine, has gained attention for its potential in modulating both IOP and neurodegeneration through diverse cellular pathways. This review evaluates the therapeutic relevance of melatonin in glaucoma by examining its mechanistic actions and emerging delivery approaches. Methods: A comprehensive literature search was conducted via PubMed and Medline to identify studies published between 2000 and 2025 on melatonin’s roles in glaucoma. Included articles discussed its effects on IOP regulation, RGC survival, oxidative stress, mitochondrial integrity, and inflammation. Results: Evidence supports melatonin’s involvement in IOP reduction via MT receptor activation and its synergism with adrenergic and enzymatic regulators. Moreover, it protects RGCs by mitigating oxidative stress, preventing mitochondrial dysfunction, and inhibiting apoptotic and inflammatory cascades. Recent advances in ocular drug delivery systems enhance its bioavailability and therapeutic potential. Conclusions: Melatonin represents a multi-target candidate for glaucoma treatment. Further clinical studies are necessary to establish optimal dosing strategies, delivery methods, and long-term safety in patients. Full article

Background/Objectives: The loss of retinal ganglion cells (RGCs) is a hallmark of glaucoma, a major cause of blindness. Glial cell activation due to increased intraocular pressure (IOP) significantly contributes to RGC death. Therefore, substances with anti-inflammatory properties could help prevent that process. This study investigated whether combining Citicoline and Coenzyme Q10 (CoQ10) can reduce glial activation in the retina and the rest of the visual pathway, potentially preventing neurodegeneration in a mouse model of unilateral laser-induced ocular hypertension (OHT). Methods: Four groups of mice were used: vehicle (n = 12), CitiQ10 (n = 12), OHT–vehicle (n = 18), and OHT–CitiQ10 (n = 18). The administration of Citicoline and CoQ10 was performed orally once a day, initiated 15 days prior to the laser treatment and maintained post-treatment until sacrifice (3 days for retina or 7 days for the rest of the visual pathway). The retina, dorsolateral geniculate nucleus, superior colliculus, and visual cortex (V1) were immunohistochemically stained and analyzed. Results: In the laser–CitiQ10 group, the Citicoline + CoQ10 compound revealed (1) an IOP decrease at 24 h and 3 days post-laser; and (2) reduced signs of macroglial (decreased GFAP area) and microglial (soma size, arbor area, microglia number, P2RY12 expression) activation in the retina and in the rest of the visual pathway (reduced activated microglial phenotypes and lower GFAP expression). Conclusions: This study shows that oral administration of Citicoline and CoQ10 can reduce glial activation caused by increased IOP in retina and visual pathway in a mouse model of OHT, potentially protecting RGCs from OHT-induced inflammation. Full article

(1) Background: Glaucoma is a multifactorial group of diseases characterized by progressive optic neuropathy. Intraocular pressure (IOP) is the only successfully modifiable risk factor for all forms of glaucoma. However, recent research has highlighted the reduction of oxidative stress and neuroinflammation as promising therapeutic targets. In this study, we evaluated the antiglaucomatous effects of a combined herbal extract applied as eye drops in a rat model of glaucoma. (2) Methods: Sprague Dawley rats were divided into four groups: healthy controls, glaucomatous animals treated with preservative-free artificial tears, and healthy and glaucomatous groups receiving combined herbal-based eye drops for 8 weeks. Glaucoma was induced through injection of microbeads into the anterior chamber at week 1 and week 3. Before the first injection and at weeks 4 and 8, rats underwent optical coherence tomography (OCT) and electroretinogram (ERG) recordings. Retinal analyses were conducted to assess retinal ganglion cell (RGC) count, vessel density, and markers of neural pathways, oxidative stress, and inflammation. (3) Results: The combination of herbal extracts showed beneficial effects on IOP elevation, and significantly improved ERG responses. Neuroprotective effects were assessed using OCT, immunohistochemistry, and proteomics. Most parameters in herbal eye drop-treated rats were not statistically different from those in healthy controls. (4) Conclusions: Topical administration of plant-based compounds may serve as an effective supportive therapy for ocular hypertension and retinal neuroprotection. Full article

We recently showed, in a mouse optic nerve crush model, that a sustained cell-based intravitreal administration of ciliary neurotrophic factor (CNTF) and glial cell line-derived neurotrophic factor (GDNF) synergistically slowed the lesion-induced degeneration of retinal ganglion cells (RGCs), resulting in the presence of approximately 35% viable RGCs eight months after the lesion. However, the combinatorial neuroprotective treatment was initiated shortly after the lesion. To mimic a more clinically relevant situation, we co-administered both factors either three or five days after an intraorbital nerve crush when approximately 35% or 57% of the RGCs were degenerated, respectively. Analyses of the retinas at different time points after the lesion consistently revealed the presence of significantly more surviving RGCs in retinas co-treated with CNTF and GDNF than in retinas treated with either factor alone. For example, when the neurotrophic factors were administered five days after the nerve crush and the animals were analyzed two months after the lesion, retinas co-treated with CNTF and GDNF contained approximately 40% of the RGCs present at the start of treatment. In comparison, monotherapy with either CNTF or GDNF protected only about 15% or 10% of the RGCs present at baseline, respectively. The number of regenerating axons in the distal nerve stumps was similar in CNTF- and CNTF/GDNF-treated animals, despite the significantly higher number of rescued RGCs in the latter group. These findings have potential implications for studies aimed at developing neuroprotective treatments for optic neuropathies such as glaucoma. Full article

Retinal ischemic disorders present significant threats to vision, characterized by inadequate blood supply oxygen–glucose deprivation (OGD), oxidative stress, and cellular injury, often resulting in irreversible injury. Catalpol, an iridoid glycoside derived from Rehmannia glutinosa, has demonstrated antioxidative and neuroprotective effects. This study aimed at investigating the protective effects and mechanisms of catalpol against oxidative stress or OGD in vitro and retinal ischemia in vivo, focusing on the modulation of key biomarkers of retinal ischemia, including HIF-1α, vascular endothelial growth factor (VEGF), angiopoietin-2, MCP-1, and the Wnt/β-catenin pathway. Cellular viability was assessed using retinal ganglion cell-5 (RGC-5) cells cultured in DMEM; a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed. H₂O₂ (1 mM)/OGD was utilized. Vehicle or different catalpol concentrations were administered 15 min before the ischemic-like insults. The Wistar rat eyes’ intraocular pressure was increased to 120 mmHg for 60 min to induce retinal ischemia. Intravitreous injections of catalpol (0.5 or 0.25 mM), Wnt inhibitor DKK1 (1 μg/4 μL), anti-VEGF Lucentis (40 μg/4 μL), or anti-VEGF Eylea (160 μg/4 μL) were administered to the rats’ eyes 15 min before or after retinal ischemia. Electroretinogram (ERG), fluorogold retrograde labeling RGC, Western blotting, ELISA, RT-PCR, and TUNEL were utilized. In vitro, both H₂O₂ and OGD models significantly (p < 0.001/p < 0.001; H₂O₂ and OGD) induced oxidative stress/ischemic-like insults, decreasing RGC-5 cell viability (from 100% to 55.14 ± 2.19%/60.84 ± 4.57%). These injuries were insignificantly (53.85 ± 1.28% at 0.25 mM)/(63.46 ± 3.30% at 0.25 mM) and significantly (p = 0.003/p = 0.012; 64.15 ± 2.41%/77.63 ± 8.59% at 0.5 mM) altered by the pre-administration of catalpol, indicating a possible antioxidative and anti-ischemic effect of 0.5 mM catalpol. In vivo, catalpol had less effect at 0.25 mM for ERG amplitude ratio (median [Q1, Q3] 14.75% [12.64%, 20.48%]) and RGC viability (mean ± SE 63.74 ± 5.13%), whereas (p < 0.05 and p < 0.05) at 0.5 mM ERG’s ratio (35.43% [24.35%, 43.08%]) and RGC’s density (74.34 ± 5.10%) blunted the ischemia-associated significant (p < 0.05 and p < 0.01) reduction in ERG b-wave amplitude (6.89% [4.24%, 10.40%]) and RGC cell viability (45.64 ± 3.02%). Catalpol 0.5 mM also significantly protected against retinal ischemia supported by the increased amplitude ratio of ERG a-wave and oscillatory potential, along with recovering a delayed a-/b-wave response time ratio. When contrasted with DKK1 or Lucentis, catalpol exhibited similar protective effects against retinal ischemia via significantly (p < 0.05) blunting the ischemia-induced overexpression of β-catenin, VEGF, or angiopoietin-2. Moreover, ischemia-associated significant increases in apoptotic cells in the inner retina, inflammatory biomarker MCP-1, and ischemic indicator HIF-1α were significantly nullified by catalpol. Catalpol demonstrated antiapoptotic, anti-inflammatory, anti-ischemic (in vivo retinal ischemia or in vitro OGD), and antioxidative (in vitro) properties, counteracting retinal ischemia via suppressing upstream Wnt/β-catenin and inhibiting downstream HIF-1α, VEGF, and angiopoietin-2, together with its decreasing TUNEL apoptotic cell number and inflammatory MCP-1 concentration. Full article

Purpose: The aim of this study was to investigate the protective effects of systemically administered tauroursodeoxycholic acid (TUDCA) in an optic nerve crush (ONC) mouse model of retinal ganglion cell (RGC) death. Methods: C57BL/6J mice were injected intraperitoneally (i.p.) three times per week with TUDCA (500 mg/kg) for two weeks, after which unilateral ONC was performed. A control cohort was identically treated with a drug vehicle (phosphate buffered saline; PBS). A separate cohort did not undergo any injections or surgeries (this was termed the “Naïve” group). Pattern electroretinography (PERG) was recorded 3 days after ONC. Retinas were harvested for whole-mount immunofluorescence staining with an antibody against RGC marker Brn3a and imaged by fluorescent confocal microscopy. Apoptotic cells in the ganglion cell layer (GCL) were detected by Terminal Deoxynucleotidyl Transferase-Mediated dUTP Nick End Labeling (TUNEL) performed on fixed retina sections. Glial fibrillary acidic protein (GFAP) immunostaining on fixed retina sections was conducted to detect the activation of Müller cells. Total RNA was extracted from retinas and expression of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-10 was determined by digital droplet PCR (ddPCR). Results: TUDCA treatment preserved visual function as assessed by PERG. P1 and N2 amplitudes from the PBS-treated ONC group were significantly diminished compared to those of the Naïve group (p < 0.001). TUDCA treatment prevented this diminution. The amplitudes of P1 and N2 in the TUDCA-treated ONC group were statistically indistinguishable from those of the Naïve group and were higher than the PBS-treated ONC group (TUDCA+ONC vs. PBS+ONC, P1: 6.99 ± 0.89 µV vs. 3.60 ± 0.69 µV, p < 0.01; N2: −9.30 (IQR: −13.43–−6.44) µV vs. −4.47 (IQR: −10.26–−2.17) µV). TUDCA treatment preserved RGCs. The ONC-vehicle-only group had 25% fewer RGCs (Brn3a-positive cells) than Naïve eyes (p < 0.0001). TUDCA treatment nearly completely prevented this loss, preserving all but 7.7% of the RGCs, and the number of RGCs in the TUDCA-treated ONC group was significantly higher than in the PBS-treated ONC group (TUDCA+ONC vs. PBS+ONC, 1738.00 ± 14.43 cells per field vs. 1454.00 ± 6.55 cells per field, p < 0.0001). The number of TUNEL-positive cells in the GCL (Naïve vs. PBS+ONC group: 1.00 (IQR: 0.00–2.00) % vs. 37.00 (IQR: 8.50–48.50) %, p < 0.05) and GFAP-positive fibers transversing retina sections (Naïve vs. PBS+ONC group: 33.00 ± 1.15 vs. 185.70 ± 42.37 fibers/retina, p < 0.05), and the expression of IL-6, TNF-α were significantly greater in the PBS-treated ONC group compared to that of the Naïve group (Naïve vs. PBS+ONC group, IL-6: 0.07 (IQR: 0.06–0.31) vs. 0.99 (IQR: 0.56–1.47), p < 0.05, TNF-α: 0.19 ± 0.069 vs. 1.39 ± 0.23; p < 0.01), an increase not observed with TUDCA treatment. Conclusions: Systemic TUDCA treatment significantly preserved RGC function and survival in the mouse ONC model of RGC damage. TUDCA treatment prevented RGC apoptosis, Müller glial cell activation, and retinal expression of several inflammatory cytokines. These data suggest that TUDCA is a promising therapeutic candidate for preserving RGC numbers and function. Full article