Comparative evaluation of four Lycium barbarum cultivars on NaIO3-induced retinal degeneration mice via multivariate statistical analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Lycium barbarum L. (goji berry) is a traditional Chinese medicine and is often used to improve vision. While various goji cultivars may differentially treat retinal degeneration, however their comparative effectiveness remains unclear. AIM OF THE STUDY: To evaluate the protective effects of four goji cultivars on NaIO3-induced retinal degeneration mouse model and identify the most therapeutically potent cultivar. MATERIALS AND METHODS: The principal compounds in the extracts of four goji cultivars were characterized by UPLC-Q-TOF/MS. A retinal degeneration mouse model was established via NaIO3 injection. Dark-light transition and TUNEL assays were used to assess visual function and retinal apoptosis. The levels of antioxidative, inflammatory, and angiogenic markers in serums and eyeballs were measured. Hierarchical cluster analysis, principal component analysis and partial least squares-discriminant analysis were used to objectively compare the treatment responses. RESULTS: Sixteen compounds were identified in goji berry extracts. All goji berry extracts could reverse NaIO3-induced visual impairment, retinal damage and apoptosis. The samples from the cultivar of Ningqi No.1 significantly modulated oxidative stress, inflammation, and vascular endothelial growth factor levels, which are more effectively than the other cultivars based on integrated multivariate profiling. CONCLUSION: Ningqi No.1 demonstrated a stronger protective effect on mouse retina than other goji cultivars, and is a potential variety for further research on the treatment of retinal degeneration.

Neuroprotective Effect of Tauroursodeoxycholic Acid (TUDCA) on In Vitro and In Vivo Models of Retinal Disorders: A Systematic Review.

BACKGROUND: Tauroursodeoxycholic acid (TUDCA) is a naturally produced hydrophilic bile acid that has been used for centuries in Chinese medicine. Numerous recent in vitro and in vivo studies have shown that TUDCA has neuroprotective action in various models of retinal disorders. OBJECTIVE: To systematically review the scientific literature and provide a comprehensive summary on the neuroprotective action and the mechanisms involved in the cytoprotective effects of TUDCA. METHODS: A systematic review was conducted in accordance with the PRISMA (The Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Systematic literature search of United States National Library of Medicine (PubMed), Web of Science, Embase, Scopus and Cochrane Library was performed, which covered all original articles published up to July 2022. The terms, "TUDCA" in combination with "retina", "retinal protection", "neuroprotection" were searched. Possible biases were identified with the adopted SYRCLE's tool. RESULTS: Of the 423 initially gathered studies, 24 articles met inclusion/exclusion criteria for full-text review. Six of them were in vitro experiments, 17 studies reported in vivo data and one study described both in vitro and in vivo data. The results revealed the effect of TUDCA on different retinal diseases, such as retinitis pigmentosa (RP), diabetic retinopathy (DR), retinal degeneration (RD), retinal gangli on cell (RGC) damage, Leber's hereditary optic neuropathy (LHON), choroidal neovascularization (CNV), and retinal detachment (RDT). The quality scores of the in vivo studies were ranged from 5 to 7 points (total 10 points), according to SYRCLE's risk of bias tool. Both in vitro and in vivo data suggested that TUDCA could effectively delay degeneration and apoptosis of retinal neurons, preserve retinal structure and function, and its mechanism of actions might be related with inhibiting apoptosis, decreasing inflammation, attenuating oxidative stress, suppressing endoplasmic reticulum(ES) stress, and reducing angiogenesis. CONCLUSION: This systematic review demonstrated that TUDCA has neuroprotective effect on in vivo and in vitro models of retinal disorders, reinforcing the currently available evidence that TUDCA could be a promising therapeutic agent in retinal diseases treatment. However, well designed clinical trials are necessary to appraise the efficacy of TUDCA in clinical setting.

Retinitis Pigmentosa: Novel Therapeutic Targets and Drug Development.

Retinitis pigmentosa (RP) is a heterogeneous group of hereditary diseases characterized by progressive degeneration of retinal photoreceptors leading to progressive visual decline. It is the most common type of inherited retinal dystrophy and has a high burden on both patients and society. This condition causes gradual loss of vision, with its typical manifestations including nyctalopia, concentric visual field loss, and ultimately bilateral central vision loss. It is one of the leading causes of visual disability and blindness in people under 60 years old and affects over 1.5 million people worldwide. There is currently no curative treatment for people with RP, and only a small group of patients with confirmed RPE65 mutations are eligible to receive the only gene therapy on the market: voretigene neparvovec. The current therapeutic armamentarium is limited to retinoids, vitamin A supplements, protection from sunlight, visual aids, and medical and surgical interventions to treat ophthalmic comorbidities, which only aim to slow down the progression of the disease. Considering such a limited therapeutic landscape, there is an urgent need for developing new and individualized therapeutic modalities targeting retinal degeneration. Although the heterogeneity of gene mutations involved in RP makes its target treatment development difficult, recent fundamental studies showed promising progress in elucidation of the photoreceptor degeneration mechanism. The discovery of novel molecule therapeutics that can selectively target specific receptors or specific pathways will serve as a solid foundation for advanced drug development. This article is a review of recent progress in novel treatment of RP focusing on preclinical stage fundamental research on molecular targets, which will serve as a starting point for advanced drug development. We will review the alterations in the molecular pathways involved in the development of RP, mainly those regarding endoplasmic reticulum (ER) stress and apoptotic pathways, maintenance of the redox balance, and genomic stability. We will then discuss the therapeutic approaches under development, such as gene and cell therapy, as well as the recent literature identifying novel potential drug targets for RP.

Combined pulses of light and sound in the retina with nutraceuticals may enhance the recovery of foveal holes.

The present manuscript stems from evidence, which indicates that specific wavelength produce an activation of the autophagy pathway in the retina. These effects were recently reported to synergize with the autophagy-inducing properties of specific phytochemicals. The combined administration of photo-modulation and phytochemicals was recently shown to have a strong potential in eliciting the recovery in the course of retinal degeneration and it was suggested as a non-invasive approach named "Lugano protocol" to treat age-related macular degeneration (AMD). Recent translational findings indicate that the protective role of autophagy may extend also to acute neuronal injuries including traumatic neuronal damage. At the same time, very recent investigations indicate that autophagy activation and retinal anatomical recovery may benefit from sound exposure. Therefore, in the present study, the anatomical rescue of a traumatic neuronal loss at macular level was investigated in a patient with idiopathic macular hole by using a combined approach of physical and chemical non-invasive treatments. In detail, light exposure was administered in combination with sound pulses to the affected retina. This treatment was supplemented by phytochemicals known to act as autophagy inducers, which were administered orally for 6 months. This combined administration of light and sound with nutraceuticals reported here as Advanced Lugano's Protocol (ALP) produced a remarkable effect in the anatomical architecture of the retina affected by the macular hole. The anatomical recovery was almost complete at roughly one year after diagnosis and beginning of treatment. The structural healing of the macular hole was concomitant with a strong improvement of visual acuity and the disappearance of metamorphopsia. The present findings are discussed in the light of a synergism shown at neuronal level between light and sound in the presence of phytochemicals to stimulate autophagy and promote proliferation and neuronal differentiation of retinal stem cells.

Cell-specific electrical stimulation of human retinal neurons assessed by pupillary response dynamics in vivo.

Studies on the electrical excitability of retinal neurons show that photoreceptors and other cell types can be selectively activated by distinct stimulation frequencies in vitro. Yet, this principle still needs to be validated in humans in vivo. As a first step, this study explored the frequency preferences of human rods by means of transcorneal electrostimulation (TES), using the electrically-elicited pupillary responses (EEPRs) as an objective readout. The stimulation paradigm contained a 1.2 Hz sinusoidal envelope, which was superimposed on variable carrier frequencies (4-30 Hz). These currents were delivered to one of the participant's eyes via a corneal electrode and consensual pupillary reactions were recorded from the contralateral eye. The responsiveness of the retina at each frequency was assessed based on the EEPR dynamics. Differences between healthy participants and patients with retinitis pigmentosa were evaluated to identify the preferred frequency range of rods. The responsiveness of healthy individuals revealed a clear peak around 6-8 Hz. In contrast, the pupillary responses of patients were significantly reduced in the lower frequency range. These findings suggest that the responses in this frequency bin were selectively mediated by rods. This work provides evidence that different retinal cell types can be selectively activated via TES in vivo, and that this effect can be captured noninvasively using EEPRs. This knowledge may be exploited for the diagnostics and therapy of retinal diseases, e.g., to design cell-specific functional tests for the degenerating retina, or to optimize stimulation paradigms which are currently used by retinal prostheses.

Large Benefit from Simple Things: High-Dose Vitamin A Improves RBP4-Related Retinal Dystrophy.

Inherited retinal diseases (IRD) are a group of heterogeneous disorders, most of which lead to blindness with limited therapeutic options. Pathogenic variants in RBP4, coding for a major blood carrier of retinol, retinol-binding protein 4, are responsible for a peculiar form of IRD. The aim of this study was to investigate if retinal function of an RBP4-related IRD patient can be improved by retinol administration. Our patient presented a peculiar white-dot retinopathy, reminiscent of vitamin A deficient retinopathy. Using a customized next generation sequencing (NGS) IRD panel we discovered a novel loss-of-function homozygous pathogenic variant in RBP4: c.255G >A, p.(Trp85*). Western blotting revealed the absence of RBP4 protein in the patient's serum. Blood retinol levels were undetectable. The patient was put on a high-dose oral retinol regimen (50,000 UI twice a week). Subjective symptoms and retinal function markedly and sustainably improved at 5-months and 1-year follow-up. Here we show that this novel IRD case can be treated by oral retinol administration.

Riboflavin deficiency leads to irreversible cellular changes in the RPE and disrupts retinal function through alterations in cellular metabolic homeostasis.

Ariboflavinosis is a pathological condition occurring as a result of riboflavin deficiency. This condition is treatable if detected early enough, but it lacks timely diagnosis. Critical symptoms of ariboflavinosis include neurological and visual manifestations, yet the effects of flavin deficiency on the retina are not well investigated. Here, using a diet induced mouse model of riboflavin deficiency, we provide the first evidence of how retinal function and metabolism are closely intertwined with riboflavin homeostasis. We find that diet induced riboflavin deficiency causes severe decreases in retinal function accompanied by structural changes in the neural retina and retinal pigment epithelium (RPE). This is preceded by increased signs of cellular oxidative stress and metabolic disorder, in particular dysregulation in lipid metabolism, which is essential for both photoreceptors and the RPE. Though many of these deleterious phenotypes can be ameliorated by riboflavin supplementation, our data suggests that some patients may continue to suffer from multiple pathologies at later ages. These studies provide an essential cellular and mechanistic foundation linking defects in cellular flavin levels with the manifestation of functional deficiencies in the visual system and paves the way for a more in-depth understanding of the cellular consequences of ariboflavinosis.

Cynaroside protects the blue light-induced retinal degeneration through alleviating apoptosis and inducing autophagy in vitro and in vivo.

BACKGROUND: Blue light can directly penetrate the lens and reach the retina to induce retinal damage, causing dry age-related macular degeneration (dAMD). Cynaroside (Cyn), a flavonoid glycoside, was proved to alleviate the oxidative damage of retinal cells in vitro. However, whether or not Cyn also exerts protective effect on blue light-induced retinal degeneration and its mechanisms of action are unclear. PURPOSE: This study aims to evaluate the protective effects of Cyn against blue-light induced retinal degeneration and its underlying mechanisms in vitro and in vivo. STUDY DESIGN/METHODS: Blue light-induced N-retinylidene-N-retinylethanolamine (A2E)-laden adult retinal pigment epithelial-19 (ARPE-19) cell damage and retinal damage in SD rats were respectively used to evaluate the protective effects of Cyn on retinal degeneration in vitro and in vivo. MTT assay and AnnexinV-PI double staining assay were used to evaluate the in vitro efficacy. Histological analysis, TUNEL assay, and fundus imaging were conducted to evaluate the in vivo efficacy. ELISA assay, western blot, and immunostaining were performed to investigate the mechanisms of action of Cyn. RESULTS: Cyn decreased the blue light-induced A2E-laden ARPE-19 cell damage and oxidative stress. Intravitreal injection of Cyn (2, 4 µg/eye) reversed the retinal degeneration induced by blue light in SD rats. Furthermore, Cyn inhibited the nuclear translocation of NF-κB and induced autophagy, which led to the clearance of overactivated pyrin domain containing 3 (NLRP3) inflammasome in vitro and in vivo. CONCLUSION: Cyn protects against blue light-induced retinal degeneration by modulating autophagy and decreasing the NLRP3 inflammasome.

Absence of Genotype/Phenotype Correlations Requires Molecular Diagnostic to Ascertain Stargardt and Stargardt-Like Swiss Patients.

We genetically characterized 22 Swiss patients who had been diagnosed with Stargardt disease after clinical examination. We identified in 11 patients (50%) pathogenic bi-allelic ABCA4 variants, c.1760+2T>C and c.4496T>C being novel. The dominantly inherited pathogenic ELOVL4 c.810C>G p.(Tyr270*) and PRPH2-c.422A>G p.(Tyr141Cys) variants were identified in eight (36%) and three patients (14%), respectively. All patients harboring the ELOVL4 c.810C>G p.(Tyr270*) variant originated from the same small Swiss area, identifying a founder mutation. In the ABCA4 and ELOVL4 cohorts, the clinical phenotypes of "flecks", "atrophy", and "bull"s eye like" were observed by fundus examination. In the small number of patients harboring the pathogenic PRPH2 variant, we could observe both "flecks" and "atrophy" clinical phenotypes. The onset of disease, progression of visual acuity and clinical symptoms, inheritance patterns, fundus autofluorescence, and optical coherence tomography did not allow discrimination between the genetically heterogeneous Stargardt patients. The genetic heterogeneity observed in the relatively small Swiss population should prompt systematic genetic testing of clinically diagnosed Stargardt patients. The resulting molecular diagnostic is required to prevent potentially harmful vitamin A supplementation, to provide genetic counseling with respect to inheritance, and to schedule appropriate follow-up visits in the presence of increased risk of choroidal neovascularization.

[Transcorneal electrostimulation in retinitis pigmentosa : Protocol of a multicentric prospective, randomized, controlled and double-masked trial on behalf of the Joint Federal Committee (G-BA pilot regulation)]. / Transkorneale Elektrostimulation bei Retinitis pigmentosa : Prüfplan einer multizentrischen, prospektiven, randomisierten, kontrollierten und doppelblinden Studie im Auftrag des Gemeinsamen Bundesausschusses (G-BA-Erprobungsrichtlinie).

The focus of this large multicenter trial commissioned by the Joint Federal Committee (Gemeinsamer Bundesausschuss, G­BA) is to determine a benefit of transcorneal electrical stimulation for retinitis pigmentosa (RP) patients. The main criterion for benefit is the kinetic visual field and whether the deterioration progresses more slowly in the study eyes compared to the sham-stimulated fellow eyes over a treatment period of 3 years.

Retinal Neurodegeneration: Correlation between Nutraceutical Treatment and Animal Model.

Retinal diseases can be induced by a variety of factors, including gene mutations, environmental stresses and dysmetabolic processes. The result is a progressive deterioration of visual function, which sometimes leads to blindness. Many treatments are under investigation, though results are still mostly unsatisfactory and restricted to specific pathologies, particularly in the case of gene therapy. The majority of treatments have been tested in animal models, but very few have progressed to human clinical trials. A relevant approach is to study the relation between the type of treatments and the degenerative characteristics of the animal model to better understand the effectiveness of each therapy. Here we compare the results obtained from different animal models treated with natural compounds (saffron and naringenin) to anticipate the potentiality of a single treatment in different pathologies.

Glial Cell Activation and Oxidative Stress in Retinal Degeneration Induced by ß-Alanine Caused Taurine Depletion and Light Exposure.

We investigate glial cell activation and oxidative stress induced by taurine deficiency secondary to ß-alanine administration and light exposure. Two months old Sprague-Dawley rats were divided into a control group and three experimental groups that were treated with 3% ß-alanine in drinking water (taurine depleted) for two months, light exposed or both. Retinal and external thickness were measured in vivo at baseline and pre-processing with Spectral-Domain Optical Coherence Tomography (SD-OCT). Retinal cryostat cross sections were immunodetected with antibodies against various antigens to investigate microglial and macroglial cell reaction, photoreceptor outer segments, synaptic connections and oxidative stress. Taurine depletion caused a decrease in retinal thickness, shortening of photoreceptor outer segments, microglial cell activation, oxidative stress in the outer and inner nuclear layers and the ganglion cell layer and synaptic loss. These events were also observed in light exposed animals, which in addition showed photoreceptor death and macroglial cell reactivity. Light exposure under taurine depletion further increased glial cell reaction and oxidative stress. Finally, the retinal pigment epithelial cells were Fluorogold labeled and whole mounted, and we document that taurine depletion impairs their phagocytic capacity. We conclude that taurine depletion causes cell damage to various retinal layers including retinal pigment epithelial cells, photoreceptors and retinal ganglion cells, and increases the susceptibility of the photoreceptor outer segments to light damage. Thus, beta-alanine supplements should be used with caution.

Restoring Color Perception to the Blind: An Electrical Stimulation Strategy of Retina in Patients with End-stage Retinitis Pigmentosa.

PURPOSE: Bioelectronic retinal prostheses that stimulate the remaining inner retinal neurons, bypassing degenerated photoreceptors, have been demonstrated to restore some vision in patients blinded by retinitis pigmentosa (RP). These implants encode luminance of the visual scene into electrical stimulation, however, leaving out chromatic information. Yet color plays an important role in visual processing when it comes to recognizing objects and orienting to the environment, especially at low spatial resolution as generated by current retinal prostheses. In this study, we tested the feasibility of partially restoring color perception in blind RP patients, with the aim to provide chromatic information as an extra visual cue. DESIGN: Case series. PARTICIPANTS: Seven subjects blinded by advanced RP and monocularly fitted with an epiretinal prosthesis. METHODS: Frequency-modulated electrical stimulation of retina was tested. Phosphene brightness was controlled by amplitude tuning, and color perception was acquired using the Red, Yellow, Green, and Blue (RYGB) hue and saturation scaling model. MAIN OUTCOME MEASURES: Brightness and color of the electrically elicited visual perception reported by the subjects. RESULTS: Within the tested parameter space, 5 of 7 subjects perceived chromatic colors along or nearby the blue-yellow axis in color space. Aggregate data obtained from 20 electrodes of the 5 subjects show that an increase of the stimulation frequency from 6 to 120 Hz shifted color perception toward blue/purple despite a significant inter-subject variation in the transition frequency. The correlation between frequency and blue-yellow perception exhibited a good level of consistency over time and spatially matched multi-color perception was possible with simultaneous stimulation of paired electrodes. No obvious correlation was found between blue sensations and array placement or status of visual impairment. CONCLUSIONS: These findings present a strategy for the generation and control of color perception along the blue-yellow axis in blind patients with RP by electrically stimulating the retina. It could transform the current prosthetic vision landscape by leading in a new direction beyond the efforts to improve the visual acuity. This study also offers new insights into the response of our visual system to electrical stimuli in the photoreceptor-less retina that warrant further mechanistic investigation.

Roots of Lithospermum erythrorhizon promotes retinal cell survival in optic nerve crush-induced retinal degeneration.

Lithospermum erythrorhizon (L. erythrorhizon), used in traditional medicine, is a potent wound healing, anti-inflammatory and antioxidant plant. However, the effects of L. erythrorhizon on retinal degenerative diseases remain unknown. Here, we explored the protective effects of L. erythrorhizon in in vitro and in vivo retinal degeneration. We found that ethanol extract of L. erythrorhizon (EELE) and the dichloromethane fraction of L. erythrorhizon (MCLE) significantly increased cell viability under glutamate/BSO-induced excitotoxicity/oxidative stress in R28 cells. Treatment with EELE and MCLE reduced the intracellular reactive oxygen species (ROS) and the levels of apoptotic proteins, such as cleaved PARP and cleaved caspase-3. Furthermore, oral administration of EELE and MCLE in an in vivo optic nerve crush mouse model decreased RGC cell death and increased retinal thickness. The major compound between EELE and MCLE was found to be lithospermic acid A (LAA), which has been shown to prevent the elevation of ROS in R28. Therefore, EELE and MCLE have protective effects against the death of retinal cells in vitro and in vivo, and the major compound, LAA, has an antioxidant effect on retinal cells, suggesting that EELE and MCLE could be beneficial agents for retinal degenerative diseases, including glaucoma.

Protective effect of Prunella vulgaris var. L extract against blue light induced damages in ARPE-19 cells and mouse retina.

Age-related macular degeneration (AMD) is one of leading causes that induce severe visual impairment and loss in the elderly. Previous studies have suggested that blue light (BL) could induce retinal degeneration, which is a major cause of the onset and development of severe AMD. In the retinal pigment epithelium (RPE) cells, A2E, a lipofuscin fluorophore, is accumulated with aging. When A2E is exposed to BL, it is easily oxidized to A2E-epoxides, leading to oxidative stress and inflammatory response in retina. The aim of this study was to investigate protective effect of Prunella vulagris (P.V) extract against oxidative stress and inflammation caused by BL, and to elucidate the underlying mechanisms in the cultured RPE cells and balb-c mice. In both model studies, P.V extract activated NF-E2 related factor 2 (Nrf-2)/hemeoxygenase-1 (HO-1) signaling pathway, followed by inhibition of ROS/MDA production, GSH depletion and reduction in SOD activity. Furthermore, P.V extract inhibited upregulation of inflammatory related genes (interlukin (IL)-1beta, IL-6, monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor A (VEGF A)) and BL induced RPE cell death, determined by cell viability and histological analyses. The mechanism of protection against inflammation by P.V extract involves inhibition of nuclear translocation of nuclear factor kappa beta (NF-kB) along with degradation of NF-kB inhibitor alpha (IkB alpha). The results suggest that P.V extract could be a potential intervention to prevent the onset and development of severe AMD.

Aucubin, An Active Ingredient in Aucuba japonica, Prevents N-methyl-N-nitrosourea-induced Retinal Degeneration in Mice.

In the present study, we examined the potent retinoprotective effects of an ethanol-based extract of Aucuba japonica (AJE) and its active ingredient, aucubin, on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration in mice. Retinal degeneration was induced by an intraperitoneal injection of MNU (60 mg/kg). AJE (250 mg/kg) and aucubin (15 mg/kg) were orally administered for 1 week after the MNU injection. Electroretinography (ERG) and histological examinations were performed. Retinal apoptosis and oxidative DNA damage were also quantified. The retinoprotective abilities of AJE and aucubin were also assessed in primary cultured retinal cells. Morphologically, MNU induced a remarkable decrease in the outer nuclear layer, which contains photoreceptor cells. However, this layer was well preserved in the AJE- and aucubin-administered mice. The ERG responses significantly decreased in both a- and b-wave amplitudes in the MNU-injected mice. In the AJE and aucubin-treated mice, ERG responses were significantly increased. In addition, a terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay and immunohistochemical staining for 8-hydroxydeoxyguanosine (8-OHdG) revealed that both AJE and aucubin attenuated MNU-induced photoreceptor cell apoptosis and oxidative DNA damage. Furthermore, the in vitro assay also showed that AJE and aucubin have potent anti-oxidative and anti-apoptotic activities in primary cultured retinal cells. These results indicate that AJE and aucubin have potent retinoprotective effects, and that this retinoprotective activity is as a result of the potency of the bioactive compound, aucubin. These pharmacological characteristics suggest the additional application of AJE or aucubin in the treatment of patients with retinal degenerative diseases.

ß-alanine supplementation induces taurine depletion and causes alterations of the retinal nerve fiber layer and axonal transport by retinal ganglion cells.

To study the effect of taurine depletion induced by ß-alanine supplementation in the retinal nerve fiber layer (RNFL), and retinal ganglion cell (RGC) survival and axonal transport. Albino Sprague-Dawley rats were divided into two groups: one group received ß-alanine supplementation (3%) in the drinking water during 2 months to induce taurine depletion, and the other group received regular water. After one month, half of the rats from each group were exposed to light. Retinas were analyzed in-vivo using Spectral-Domain Optical Coherence Tomography (SD-OCT). Prior to processing, RGCs were retrogradely traced with fluorogold (FG) applied to both superior colliculi, to assess the state of their retrograde axonal transport. Retinas were dissected as wholemounts, surviving RGCs were immunoidentified with Brn3a, and the RNFL with phosphorylated high-molecular-weight subunit of the neurofilament triplet (pNFH) antibodies. ß-alanine supplementation decreases significantly taurine plasma levels and causes a significant reduction of the RNFL thickness that is increased after light exposure. An abnormal pNFH immunoreactivity in some RGC bodies, their proximal dendrites and axons, and a further diminution of the mean number of FG-traced RGCs compared with Brn3a+RGCs, indicate that their retrograde axonal transport is affected. In conclusion, taurine depletion causes RGC loss and axonal transport impairment. Finally, our results suggest that care should be taken when ingesting ß-alanine supplements due to the limited understanding of their potential adverse effects.

Amelioration of Mouse Retinal Degeneration After Blue LED Exposure by Glycyrrhizic Acid-Mediated Inhibition of Inflammation.

Glycyrrhizic acid (GA) is a major component in the root and rhizomes of licorice (Glycyrrhiza glabra), which have been used as an herbal medicine, because of its anti-inflammatory activity. GA is known as an inhibitor of high-mobility group box 1 (HMGB1), which is involved in the pathogenesis of various inflammatory diseases including inner retinal neuropathy. In this study, we examined the effect of GA in a mouse model of retinal degeneration (RD), the leading cause of blindness. RD was induced by exposure to a blue light-emitting diode (LED). In functional assessment, electroretinography showed that the amplitudes of both a- and b-waves were reduced in RD mice, whereas they were significantly increased in GA-treated RD mice (P < 0.05), compared to those in non-treated RD animals. In histological assessment, GA treatment preserved the outer nuclear layer where photoreceptors reside and reduced photoreceptor cell death. GA-treated retinas showed significantly reduced expression of proinflammatory cytokines such as TNF-α, IL-6, IL-1ß, CCL2 and 6, iNOS, and COX-2 (P < 0.05), compared to that in non-treated retinas. Immunohistochemistry showed that Iba-1 and GFAP expression was markedly reduced in GA-treated retinas, indicating decreased glial response and inflammation. Interestingly, HMGB1 expression was reduced in non-treated RD retinas whereas GA paradoxically increased its expression. These results demonstrate that GA preserves retinal structure and function by inhibiting inflammation in blue LED-induced RD, suggesting a potential application of GA as a medication for RD. In addition, we propose a potential retinal protective function of HMGB1 in the pathogenesis of RD.

Delay of cone degeneration in retinitis pigmentosa using a 12-month treatment with Lycium barbarum supplement.

ETHNOPHARMACOLOGICAL RELEVANCE: Lycium barbarum L. (also known as "Goji berry"), a traditional Chinese herbal medicine, has been a common herb in the traditional Chinese pharmacopoeia for centuries. The main active component is the Lycium barbarum polysaccharides and its antioxidative effect has been widely shown to provide neuroprotection to the eye, and it would, therefore, be interesting to determine if Lycium barbarum help delay vision deterioration in patients with retinitis pigmentosa. AIM OF THE STUDY: Cone rescue is a potential method for delaying deterioration of visual function in Retinitis pigmentosa (RP). This study aimed to investigate the treatment effect of Lycium barbarum L. (LB) supplement on retinal functions and structure in RP patients after a 12-month intervention trial. METHODS: The investigation was a double-masked and placebo-controlled clinical study. Each of forty-two RP subjects who completed the 12-month intervention (23 and 19 in the treatment and placebo groups respectively) received a daily supply of LB or placebo granules for oral administration. The primary outcome was change of best corrected visual acuity (VA) (90% and 10% contrast) from the baseline to the end of treatment. The secondary outcomes were sensitivity changes of the central visual field, amplitude of full-field electroretinogram (ffERG) (including scotopic maximal response and photopic cone response), and average macular thickness. RESULTS: The compliance rates for both groups exceeded 80%. There were no deteriorations of either 90% or 10% contrast VA in the LB group compared with the placebo group (p = 0.001). A thinning of macular layer was observed in the placebo group, which was not observed in the LB group (p = 0.008). However, no significant differences were found in the sensitivity of visual field or in any parameters of ffERG between the two groups. No significant adverse effects were reported in the treatment group. CONCLUSIONS: LB supplement provides a neuroprotective effect for the retina and could help delay or minimize cone degeneration in RP. CLASSIFICATIONS: Clinical Studies (1.05). TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT02244996.

Brain-Derived Neurotrophic Factor as a Treatment Option for Retinal Degeneration.

This review discusses the therapeutic potential of brain-derived neurotrophic factor (BDNF) for retinal degeneration. BDNF, nerve growth factor (NGF), neurotrophin 3 (NT-3) and NT-4/NT-5 belong to the neurotrophin family. These neuronal modulators activate a common receptor and a specific tropomyosin-related kinase (Trk) receptor. BDNF was identified as a photoreceptor protectant in models of retinal degeneration as early as 1992. However, development of effective therapeutics that exploit this pathway has been difficult due to challenges in sustaining therapeutic levels in the retina.