Optical Coherence Tomography Findings in Glaucoma With Coexisting Vitamin A Deficiency.

This case study reports on the presence of vitamin A deficiency in an adult with asymmetric normal tension glaucoma. The retinal OCT findings demonstrated not only expected loss of the outer retinal layers, typically seen in vitamin A deficiency, but also severe and bilateral loss of the inner retinal layers. After vitamin A supplementation, visual acuity, dark adaptation, and color vision normalized. The outer retinal layers had a restoration of thickness after vitamin A supplementation, but the inner layers did not change. This case is unique because it may give us an insight into the role of vitamin A on the inner retina and demonstrate the recovery of the outer retinal layers with vitamin A supplementation.

Solanum nigrum Toxicity and Its Neuroprotective Effect Against Retinal Ganglion Cell Death Through Modulation of Extracellular Matrix in a Glaucoma Rat Model.

Purpose: Glaucoma is a complex degenerative optic neuropathy characterized by loss of retinal ganglion cells (RGCs) leading to irreversible vision loss and blindness. Solanum nigrum has been used for decades in traditional medicine system. However, no extensive studies were reported on its antiglaucoma properties. Therefore, this study was designed to investigate the neuroprotective effects of S. nigrum extract on RGC against glaucoma rat model. Methods: High performance liquid chromatography and liquid chromatography tandem mass spectrometry was used to analyze the phytochemical profile of aqueous extract of S. nigrum (AESN). In vitro, {3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide} (MTT) and H2DCFDA assays were used to determine cell viability and reactive oxygen species (ROS) production in Statens Seruminstitut Rabbit Cornea cells. In vivo, AESN was orally administered to carbomer-induced rats for 4 weeks. Intraocular pressure, antioxidant levels, and electrolytes were determined. Histopathological and immunohistochemical analysis was carried out to evaluate the neurodegeneration of RGC. Results: MTT assay showed AESN exhibited greater cell viability and minimal ROS production at 10 µg/mL. Slit lamp and funduscopy confirmed glaucomatous changes in carbomer-induced rats. Administration of AESN showed minimal peripheral corneal vascularization and restored histopathological alterations such as minimal loss of corneal epithelium and moderate narrowing of the iridocorneal angle. Immunohistochemistry analysis showed increased expression of positive BRN3A cells and decreased matrix metalloproteinase (MMP)-9 activation in retina and cornea, whereas western blot analysis revealed downregulation of extracellular matrix proteins (COL-1 and MMP-9) in AESN-treated rats compared with the diseased group rats. Conclusions: AESN protects RGC loss through remodeling of MMPs and, therefore, can be used for the development of novel neurotherapeutics for the treatment of glaucoma.

Combined treatment of human mesenchymal stem cells and green tea extract on retinal ganglion cell regeneration in rats after optic nerve injury.

Retinal ganglion cell (RGC) death and axonal loss cause irreversible vision loss upon optic nerve (ON) injury. We have independently demonstrated that mesenchymal stem cells (MSCs) and green tea extract (GTE) promote RGC survival and axonal regeneration in rats with ON injury. Here we aimed to evaluate the combined treatment effect of human bone marrow-derived MSCs (hBM-MSCs) and GTE on RGC survival and axonal regeneration after ON injury. Combined treatment of hBM-MSCs and GTE promoted RGC survival and neurite outgrowth/axonal regeneration in ex vivo retinal explant culture and in rats after ON injury. GTE increased Stat3 activation in the retina after combined treatment, and enhanced brain-derived neurotrophic factor secretion from hBM-MSCs. Treatment of 10 µg/mL GTE would not induce hBM-MSC apoptosis, but inhibited their proliferation, migration, and adipogenic and osteogenic differentiation in vitro with reducing matrix metalloproteinase secretions. In summary, this study revealed that GTE can enhance RGC protective effect of hBM-MSCs, suggesting that stem cell priming could be a prospective strategy enhancing the properties of stem cells for ON injury treatment.

Vitamin B3 Supplementation for Optic Neuropathies: A Comprehensive Review.

Optic neuropathies, such as glaucoma, are some of the leading causes of irreversible blindness worldwide. There has been a lot of research for potential therapies that could attenuate and even reduce the impact of the pathological pathways that lead to the loss of retinal ganglion cells (RGCs). In recent years, vitamin B3 (nicotinamide) has gained some interest as a viable option for these neurodegenerative diseases due to its fundamental role in enhancing the mitochondria metabolism of the RGCs. This review focuses on elucidating the impact of vitamin B3 on retinal cells, especially when in a dysfunctional state like what happens in optic neuropathies, especially glaucoma. This review also summarizes the existing and future research on the clinical effects of vitamin B3 in these optic neuropathies, and determines appropriate recommendations regarding its dosing, efficacy, and eventual side effects.

Early effects of cardiopulmonary bypass surgery on retinal nerve fiber layer and ganglion cell layer.

PURPOSE: To determine the effects of cardiopulmonary bypass surgery on retinal nerve fiber layer, ganglion cell layer, and macula by optic coherens tomography (OCT). METHOD: Sixty-six eyes of 33 patients aged between 44 and 74 who were indicated for cardiopulmonary bypass surgery in the cardiovascular surgery clinic were included in the study. Routine ophthalmologic examinations of all patients were performed before and 1 week after surgery. In addition, 3D(H) Macula+5 Line Cross 12 × 9 mm mod and Peripapilar 3D Disk 6 × 6 mm mod data were analyzed with OCT (Topcon, Triton Swept Source-OKT, Tokyo, Japan) device. Peripapillary total, superior, inferior retinal nerve fiber layer (RNFL), optic disc cavity volume, cup-to-disc ratio, macular ganglion cell layer (GCL), macular thickness were compared before and after surgery. RESULTS: After cardiopulmonary bypass surgery, thickening was detected in the total RNFL (p<0.001), superior RNFL (p = 0.01) and inferior RNFL (p<0.001) layers. There was no change in the values of GCL, macular thickness, optic disc cupping volume, cup-to-disc ratio after surgery (p>0.05). There was a positive correlation (r = 0.392 p<0.05) between the patients' blood oxygen (PO2) values during bypass surgery with their post-surgical GCL+ values, and a negative correlation between optic disc cup volumes (r=-0.349 p<0.05). CONCLUSION: RNFL thickening has been detected in patients undergoing cardiopulmonary bypass surgery. This thickening may occur secondary to ischemic edema that occurs during surgery. Considering the late complications of ischemic edema in the RNFL, oxygen levels should be kept at an optimum level during surgery and long-term ophthalmologic follow-ups should be performed.

Parapapillary choroidal microvasculature dropout in eyes with primary open-angle glaucoma.

The purpose of this study was to evaluate how various parameters are related to microvasculature dropout (MvD) area measured using optical coherence tomography angiography (OCTA). We measured the area of MvD in 55 patients with primary open-angle glaucoma (POAG). Using OCTA, MvD area and peripapillary choroidal atrophy (PPA) area were assessed in a 4.5 mm × 4.5 mm region. The following were examined: circumpapillary nerve fiber layer (cpRNFL) thickness, optic disc area, optic disc cupping area, optic disc rim area, Humphrey Field Analyzer (HFA) 24/10-2 mean deviation (MD), and pattern standard deviation (PSD). The relationship between MvD area and each parameter was evaluated using Spearman's rank correlation coefficient analysis. Mean MvD area and PPA area were 0.18 ± 0.17 mm2 and 1.13 ± 0.72 mm2, respectively. MvD area was significantly correlated with optic disc rim area (p = 0.0017), cpRNFL (p = 0.0027), HFA 24/10-2 MD, and PSD (p < 0.001). In eyes with POAG, MvD area indicates the severity of glaucoma, which might be associated with structural changes in the peripapillary vasculature around the optic disc.

Herbal and Natural Treatments for the Management of the Glaucoma: An Update.

Glaucoma causes the degeneration of the retinal ganglion cells (RGCs) and their axons, inducing a tissue reshaping that affects both the retina and the optic nerve head. Glaucoma care especially focuses on reducing intraocular pressure, a significant risk factor for progressive damage to the optic nerve. The use of natural treatments, such as herbs, vitamins, and minerals, is becoming increasingly popular today. While plants are a rich source of novel biologically active compounds, only a small percentage of them have been phytochemically examined and evaluated for their medicinal potential. It is necessary for eye care professionals to inform their glaucoma patients about the therapy, protection, and efficacy of commonly used herbal medicines, considering the widespread use of herbal medicines. The purpose of this review is to examine evidence related to the most widely used herbal medicines for the management and treatment of glaucoma, to better understand the potential benefits of these natural compounds as supplementary therapy.

Efficacy of citicoline as a supplement in glaucoma patients: A systematic review.

PURPOSE: Glaucoma is a leading cause of irreversible blindness worldwide. Retinal ganglion cells (RGC), the neurons that connect the eyes to the brain, specifically die in glaucoma, leading to blindness. Elevated intraocular pressure (IOP) is the only modifiable risk factor, however, many patients progress despite excellent IOP control. Thus, alternative treatment strategies to prevent glaucoma progression are an unmet need. Citicoline has demonstrated neuroprotective properties in central neurodegenerative diseases. However, conclusive evidence of the effect of citicoline on glaucoma progression is missing. This systematic review investigates first-time the therapeutic potential of citicoline in glaucoma patients. METHODS: The present study was conducted according to the PRISMA 2020 statement. PubMed, Web of Science, Google Scholar, and Embase were accessed in July 2023 to identify all clinical studies investigating the efficacy of citicoline on IOP, the mean deviation of the 24-2 visual field testing (MD 24-2), retinal nerve fibre layer (RNFL), and the pattern electroretinogram (PERG) P50-N95 amplitude in glaucoma patients. The risk of bias was assessed using the Review Manager 5.3 software (The Nordic Cochrane Collaboration, Copenhagen) and the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tool. RESULTS: Ten studies were eligible for this systematic review, including 424 patients. The mean length of the follow-up was 12.1 ± 11.6 months. The overall risk of bias was low to moderate. The mean age of the patients was 56.7 years. There were no significant differences in the IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude between patients receiving citicoline and the control group. There was no improvement from baseline to the last follow-up in IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude. CONCLUSION: There is a lack of sufficient evidence to support that citicoline slows the progression of glaucoma.

Impact of 24-Hour Intraocular Pressure on Optic Nerve Fiber Layer Thickness in Patients with Early Diabetic Retinopathy.

Background: The optic nerve fiber layer, composed of ganglion cell axons within the ganglion cell layer, undergoes thickness changes due to diabetic retinopathy. However, the relationship between intraocular pressure (IOP) and optic fiber layer thickness remains unclear. Objective: To investigate the correlation between 24-hour intraocular pressure and optic nerve fiber layer thickness in patients with early diabetic retinopathy. Methods: This retrospective study collected 353 patients with early diabetic retinopathy from January 2019 to December 2021. They were categorized into the retinopathy group (n = 153) and the control group (n = 200). 24-hour IOP and optic fiber layer thickness were assessed, and the correlation between them was analyzed. Results: The observation group exhibited significantly higher 24-hour IOP compared to the control group (16.64 ± 2.58 vs. 15.63 ± 2.52 mmHg, P < .001). Notably, the thickness of upper, lower, nasal, temporal, and average optic nerve fiber layers in the observation group decreased significantly (P < .001). Pearson linear correlation revealed significant negative associations between 24-hour IOP and upper, nasal, temporal, and mean optic nerve fiber layer thickness (R2 = -0.277, -0.399, -0.344, and -0.489, P < .05). The upper, lower, nasal, temporal, and mean optic fiber thickness demonstrated diagnostic value for non-early diabetic retinopathy in type 2 diabetes patients (P < .05), with mean optic fiber thickness displaying the highest diagnostic potential (area under the curve: 0.843, 95% Confidence Interval: 0.803-0.884, P < .001). Conclusions: Thinning of the optic nerve fiber layer in early diabetic retinopathy patients holds predictive value for the condition and exhibits a negative correlation with 24-hour intraocular pressure.

Longitudinal Assessment of Retinal Nerve Fiber Layer and Ganglion Cell Complex Thicknesses in Patients With Large Optic Disc Cups and Normal Intraocular Pressure and Visual Fields.

PRCIS: The thicknesses of the circumpapillary retinal nerve fiber layer (cpRNFL) and ganglion cell complex (GCC) did not change during 5 years in physiological large disc cupping. PURPOSE: We evaluated longitudinal changes in the thicknesses of the cpRNFL and GCC in large disc cupping with a normal intraocular pressure (IOP) (<21 mm Hg) and visual field. METHODS: This retrospective, consecutive case series study included 269 eyes of 269 patients with large disc cupping and normal IOP. We analyzed patient demographics, IOP, central corneal thickness, vertical cup-to-disc ratios using color fundus photography, the thicknesses of the cpRNFL and GCC using RTVue-100, and mean deviation using visual field examinations. RESULTS: The differences in IOP, vertical cup-to-disc ratios, and mean deviation between the baseline and each follow-up visit were not statistically significant. The baseline average and mean average at 60 months follow-up of the cpRNFL thickness were 106.5±8.5 and 105.1±9.3 µm, respectively; differences between the baseline and each follow-up visit were not statistically significant. The baseline average and mean average at 60 months follow-up of the GCC thickness were 82.8±9. and 81.5±9.2 µm, respectively; differences between baseline and each follow-up visit were not statistically significant. CONCLUSIONS: The thicknesses of the cpRNFL and GCC did not change in well-maintained optic nerve head findings with normal IOP and visual field during a 5-year follow-up period. Optical coherence tomography evaluations of the thicknesses of the cpRNFL and GCC help accurately diagnose physiological optic disc cupping.

Early diagnosis of retinal neurovascular injury in diabetic patients without retinopathy by quantitative analysis of OCT and OCTA.

AIMS: To quantitatively analyze and compare the differences in retinal neurovascular units (NVUs) between healthy individuals and patients with type 2 diabetes mellitus (DM) by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) techniques and to determine the value of this technique for the early diagnosis of retinal neurovascular damage in patients with diabetes mellitus without retinopathy (NDR). METHODS: This observational case‒control study was conducted from July 1, 2022, to November 30, 2022, at the outpatient ophthalmology clinic of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine. All subjects underwent baseline data entry and mean thickness of the peripapillary retinal nerve fiber layer (pRNFL), the thickness of each retinal layer in the macula 3 × 3 mm, and vascular density (VD) examination. RESULTS: The study included 35 healthy individuals and 48 patients with DM. The retinal VD as well as partial pRNFL, macular nerve fiber layer (NFL), and macular ganglion cell layer (GCL) thickness in DM patients exhibited significantly lower VD in the DM group than in the control group (p < 0.05). Age and disease duration of DM patients showed a negative trend with pRNFL thickness, macular NFL thickness, macular GCL thickness, and VD. However, a positive trend was observed between DM duration and partial inner nuclear layer (INL) thickness. Moreover, there was a positive correlation between macular NFL and GCL thickness and VD for the most part, while a negative correlation was shown between INL temporal thickness and DVC-VD. pRNFL-TI and GCL-superior thickness were screened as two variables in the analysis of the predictors of retinal damage in DM according to the presence or absence of DM. The AUCs were 0.765 and 0.673, respectively. By combining the two indicators for diagnosis, the model predicted prognosis with an AUC of 0.831. In the analysis of retinal damage indicators associated with the duration of DM, after regression logistic analysis according to the duration of DM within 5 years and more than 5 years, the model incorporated two indicators, DVC-VD and pRNFL-N thickness, and the AUCs were 0.764 and 0.852, respectively. Combining the two indicators for diagnosis, the AUC reached 0.925. CONCLUSIONS: Retinal NVU may have been compromised in patients with DM without retinopathy. Basic clinical information and rapid noninvasive OCT and OCTA techniques are useful for the quantitative assessment of retinal NVU prognosis in patients with DM without retinopathy.

Calcium Imaging in Mouse Superior Colliculus.

The superior colliculus (SC), an evolutionarily conserved midbrain structure in all vertebrates, is the most sophisticated visual center before the emergence of the cerebral cortex. It receives direct inputs from ~30 types of retinal ganglion cells (RGCs), with each encoding a specific visual feature. It remains elusive whether the SC simply inherits retinal features or if additional and potentially de novo processing occurs in the SC. To reveal the neural coding of visual information in the SC, we provide here a detailed protocol to optically record visual responses with two complementary methods in awake mice. One method uses two-photon microscopy to image calcium activity at single-cell resolution without ablating the overlaying cortex, while the other uses wide-field microscopy to image the whole SC of a mutant mouse whose cortex is largely undeveloped. This protocol details these two methods, including animal preparation, viral injection, headplate implantation, plug implantation, data acquisition, and data analysis. The representative results show that the two-photon calcium imaging reveals visually evoked neuronal responses at single-cell resolution, and the wide-field calcium imaging reveals neural activity across the entire SC. By combining these two methods, one can reveal the neural coding in the SC at different scales, and such combination can also be applied to other brain regions.

Vitamin C protects retinal ganglion cells via SPP1 in glaucoma and after optic nerve damage.

Glaucoma is a common neurodegenerative disorder characterized by retinal ganglion cell death, astrocyte reactivity in the optic nerve, and vision loss. Currently, lowering the intraocular pressure (IOP) is the first-line treatment, but adjuvant neuroprotective approaches would be welcome. Vitamin C possesses neuroprotective activities that are thought to be related to its properties as a co-factor of enzymes and its antioxidant effects. Here, we show that vitamin C promotes a neuroprotective phenotype and increases gene expression related to neurotropic factors, phagocytosis, and mitochondrial ATP production. This effect is dependent on the up-regulation of secreted phosphoprotein 1 (SPP1) in reactive astrocytes via the transcription factor E2F1. SPP1+ astrocytes in turn promote retinal ganglion cell survival in a mouse model of glaucoma. In addition, oral administration of vitamin C lowers the IOP in mice. This study identifies an additional neuroprotective pathway for vitamin C and suggests a potential therapeutic role of vitamin C in neurodegenerative diseases such as glaucoma.

S-Cone Photoreceptors Regulate Daily Rhythms and Light-Induced Arousal/Wakefulness in Diurnal Grass Rats (Arvicanthis niloticus).

Beyond visual perception, light has non-image-forming effects mediated by melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). The present study first used multielectrode array recordings to show that in a diurnal rodent, Nile grass rats (Arvicanthis niloticus), ipRGCs generate rod/cone-driven and melanopsin-based photoresponses that stably encode irradiance. Subsequently, two ipRGC-mediated non-image-forming effects, namely entrainment of daily rhythms and light-induced arousal, were examined. Animals were first housed under a 12:12 h light/dark cycle (lights-on at 0600 h) with the light phase generated by a low-irradiance fluorescent light (F12), a daylight spectrum (D65) stimulating all photoreceptors, or a narrowband 480 nm spectrum (480) that maximized melanopsin stimulation and minimized S-cone stimulation (λmax 360 nm) compared to D65. Daily rhythms of locomotor activities showed onset and offset closer to lights-on and lights-off, respectively, in D65 and 480 than in F12, and higher day/night activity ratio under D65 versus 480 and F12, suggesting the importance of S-cone stimulation. To assess light-induced arousal, 3-h light exposures using 4 spectra that stimulated melanopsin equally but S-cones differentially were superimposed on F12 background lighting: D65, 480, 480 + 365 (narrowband 365 nm), and D65 - 365. Compared to the F12-only condition, all four pulses increased in-cage activity and promoted wakefulness, with 480 + 365 having the greatest and longest-lasting wakefulness-promoting effects, again indicating the importance of stimulating S-cones as well as melanopsin. These findings provide insights into the temporal dynamics of photoreceptor contributions to non-image-forming photoresponses in a diurnal rodent that may help guide future studies of lighting environments and phototherapy protocols that promote human health and productivity.

Synaptic and circuit mechanisms prevent detrimentally precise correlation in the developing mammalian visual system.

The developing visual thalamus and cortex extract positional information encoded in the correlated activity of retinal ganglion cells by synaptic plasticity, allowing for the refinement of connectivity. Here, we use a biophysical model of the visual thalamus during the initial visual circuit refinement period to explore the role of synaptic and circuit properties in the regulation of such neural correlations. We find that the NMDA receptor dominance, combined with weak recurrent excitation and inhibition characteristic of this age, prevents the emergence of spike-correlations between thalamocortical neurons on the millisecond timescale. Such precise correlations, which would emerge due to the broad, unrefined connections from the retina to the thalamus, reduce the spatial information contained by thalamic spikes, and therefore we term them 'parasitic' correlations. Our results suggest that developing synapses and circuits evolved mechanisms to compensate for such detrimental parasitic correlations arising from the unrefined and immature circuit.

[Acupuncture for glaucoma-induced optic atrophy: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of acupuncture for glaucoma-induced optic atrophy. METHODS: A total of 70 patients (89 affected eyes) with glaucoma-induced optic atrophy were randomized into an observation group and a control group, 35 cases in each group. The control group was given basic western medicine treatment. In the observation group, on the basis of the treatment in the control group, acupuncture was applied at main acupoints i.e. Baihui (GV 20), Shangjingming (Extra), Chengqi (ST 1), Fengchi (GB 20), Zusanli (ST 36), combined with supplementary acupoints based on syndrome differentiation, once every three days, twice a week. The treatment for 3 months was required in both groups. Before treatment, after treatment and in follow-up of 6 months after treatment, the best corrected visual acuity (BCVA), intraocular pressure (IOP), indexes of visual field (visual field index [VFI], mean deviation [MD], pattern standard deviation [PSD]) and mean thickness of retinal nerve fiber layer (RNFL) were observed in the two groups. RESULTS: Compared before treatment, BCVA was decreased after treatment and in follow-up in the control group (P<0.05); in the follow-up, BCVA in the observation group was higher than that in the control group (P<0.05). On each time point before and after treatment, there was no significant difference within or between the two groups (P>0.05). After treatment and in the follow-up, the mean thickness of RNFL was larger than the control group (P<0.05). CONCLUSION: On the basis of the basic western medicine treatment, acupuncture can delay the decline of vision and the thinning of retinal nerve fiber layer in patients with glaucoma-induced optic atrophy.

Multimodal investigation of melanopsin retinal ganglion cells in Alzheimer's disease.

OBJECTIVE: In Alzheimer's disease (AD), the presence of circadian dysfunction is well-known and may occur early in the disease course. The melanopsin retinal ganglion cell (mRGC) system may play a relevant role in contributing to circadian dysfunction. In this study, we aimed at evaluating, through a multimodal approach, the mRGC system in AD at an early stage of disease. METHODS: We included 29 mild-moderate AD (70.9 ± 11 years) and 26 (70.5 ± 8 years) control subjects. We performed an extensive neurophtalmological evaluation including optical coherence tomography with ganglion cell layer segmentation, actigraphic evaluation of the rest-activity rhythm, chromatic pupillometry analyzed with a new data-fitting approach, and brain functional MRI combined with light stimuli assessing the mRGC system. RESULTS: We demonstrated a significant thinning of the infero-temporal sector of the ganglion cell layer in AD compared to controls. Moreover, we documented by actigraphy the presence of a circadian-impaired AD subgroup. Overall, circadian measurements worsened by age. Chromatic pupillometry evaluation highlighted the presence of a pupil-light response reduction in the rod condition pointing to mRGC dendropathy. Finally, brain fMRI showed a reduced occipital cortex activation with blue light particularly for the sustained responses. INTERPRETATION: Overall, the results of this multimodal innovative approach clearly document a dysfunctional mRGC system at early stages of disease as a relevant contributing factor for circadian impairment in AD providing also support to the use of light therapy in AD.

Discriminating Between Compressive Optic Neuropathy With Glaucoma-Like Cupping and Glaucomatous Optic Neuropathy Using OCT and OCTA.

Purpose: To discriminate between compressive optic neuropathy with glaucoma-like cupping (GL-CON) and glaucomatous optic neuropathy (GON) by comparing the peripapillary retinal nerve fiber layer (pRNFL) thickness and retinal microvasculature using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Methods: In this retrospective cross-sectional study, OCT scans were performed on 28 eyes of GL-CON, 34 eyes of GON, and 41control eyes to determine the pRNFL thickness, ganglion cell complex thickness, and cup/disc ratio. OCTA scans were conducted for 12 eyes of GL-CON, 15 eyes of GON, and 15 control eyes to measure the vessel density of the peripapillary and macular areas. Analysis of covariance was used to perform the comparisons, and the area under the curve was calculated. Results: The GON eyes had a significantly thinner pRNFL in the inferior quadrant and greater vertical cup/disc ratio than the GL-CON eyes. In the radial peripapillary capillary segment, the vessel density of the GON in the inferior sectors was significantly lower than in the GL-CON. The superficial macular vessel density in the whole-image, peritemporal, perinasal, and peri-inferior sectors was significantly smaller in the GON group than in the GL-CON group. The best parameter for discriminating between GL-CON and GON was the superficial macular vessel density in the peritemporal sector. Conclusions: GL-CON eyes showed a characteristic pattern of pRNFL and retinal microvascular changes. Translational Relevance: GL-CON can be effectively distinguished from GON by detecting the alterations in the pRNFL and retinal microvasculature using OCT and OCTA.

Green tea extract enhances retinal ganglion cell survival and axonal regeneration in rats with optic nerve injury.

Current clinical treatments have not yet effectively cured progressive retinal ganglion cell (RGC) death and axonal degeneration after optic nerve (ON) injury. We previously demonstrated green tea extract (GTE) can reduce RGC death in rats after ischemic injury. Here, we aim to determine the prophylactic and therapeutic effects and mechanisms of GTE on RGC survival and axonal regeneration in rats with ON injury. GTE (275 or 550 mg/kg) was administered intragastrically for 7 d before or 14 d post-ON crush surgery in adult Fischer 344 rats. Rats with pre- or post-operative treatment of 275 mg/kg GTE showed significantly higher numbers of RGCs and regenerated axons post-ON injury with improved pupillary light reflex as compared to saline-treated rats. Akt and Erk p42/44 activation was higher in the retina of rats given 275 mg/kg GTE pre-surgery, whereas Stat3 activation was higher in those with 275 mg/kg GTE post-operation. Less activated microglia were observed in rats with pre-treatment of 275 or 550 mg/kg GTE. RNA sequencing analysis identified the downregulation of inflammation, apoptosis, and microglia activation genes in the retina of rats with pre- or post-treatment with 275 mg/kg GTE as compared to the saline-treated rats. In summary, this study revealed the prophylactic and therapeutic treatment effects of GTE on RGC survival and axonal regeneration in rats with ON injury, indicating a potential alternative treatment for traumatic optic neuropathy.

Light modulates glucose metabolism by a retina-hypothalamus-brown adipose tissue axis.

Public health studies indicate that artificial light is a high-risk factor for metabolic disorders. However, the neural mechanism underlying metabolic modulation by light remains elusive. Here, we found that light can acutely decrease glucose tolerance (GT) in mice by activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) innervating the hypothalamic supraoptic nucleus (SON). Vasopressin neurons in the SON project to the paraventricular nucleus, then to the GABAergic neurons in the solitary tract nucleus, and eventually to brown adipose tissue (BAT). Light activation of this neural circuit directly blocks adaptive thermogenesis in BAT, thereby decreasing GT. In humans, light also modulates GT at the temperature where BAT is active. Thus, our work unveils a retina-SON-BAT axis that mediates the effect of light on glucose metabolism, which may explain the connection between artificial light and metabolic dysregulation, suggesting a potential prevention and treatment strategy for managing glucose metabolic disorders.