The ameliorating effects of adipose-derived stromal vascular fraction cells on blue light-induced rat retinal injury via modulation of TLR4 signaling, apoptosis, and glial cell activity.

Blue light (BL)-induced retinal injury has become a very common problem due to over exposure to blue light-emitting sources. This study aimed to investigate the possible ameliorating impact of stromal vascular fraction cells (SVFCs) on BL-induced retinal injury. Forty male albino rats were randomly allocated into four groups. The control group rats were kept in 12-h light/12-h dark. Rats of SVFC-control as the control group, but rats were intravenously injected once by SVFCs. Rats of both the BL-group and BL-SVFC group were exposed to BL for 2 weeks; then rats of the BL-SVFC group were intravenously injected once by SVFCs. Following the BL exposure, rats were kept for 8 weeks. Physical and physiological studies were performed; then retinal tissues were collected for biochemical and histological studies. The BL-group showed physical and physiological changes indicating affection of the visual function. Biochemical marker assessment showed a significant increase in MDA, TLR4 and MYD88 tissue levels with a significant decrease in TAC levels. Histological and ultrastructural assessment showed disruption of the normal histological architecture with retinal pigment epithelium, photoreceptors, and ganglion cell deterioration. A significant increase in NF-κB, caspase-3, and GFAP immunoreactivity was also detected. BL-SVFC group showed a significant improvement in physical, physiological, and biochemical parameters. Retinal tissues revealed amelioration of retinal structural and ultrastructural deterioration and a significant decrease in NF-κB and caspase-3 immunoreactivity with a significant increase in GFAP immunoreaction. This study concluded that SVFCs could ameliorate the BL-induced retinal injury through TLR-4/MYD-88/NF-κB signaling inhibition, regenerative, anti-oxidative, and anti-apoptotic effects.

Retinal injury mouse model and pathophysiological assessment of the effect of arsenical vesicants.

The eye is ten times more vulnerable to chemical warfare agents than other organs. Consistently, exposure to vesicant arsenical lewisite (LEW) manifests significant corneal damage leading to chronic inflammation, corneal opacity, vascularization, and edema, culminating in corneal cell death. However, despite the progress has made in the research field investigating arsenical-induced pathogenesis of the anterior chamber of the eye, the retinal damage resulted from exposure to arsenicals has not been identified yet. Therefore, we investigated the effects of direct ocular exposure (DOE) to LEW and phenylarsine oxide (PAO) on the retina. DOE to arsenicals was conducted using the vapor cap method at the MRIGlobal facility or an eye patch soaked in solutions with different PAO concentrations at UAB. Animals were assessed at 1, 3, 14, and 28 days postexposure. Results of the study demonstrated that both arsenicals cause severe retinal damage, activating proinflammatory programs and launching apoptotic cell death. Moreover, the DOE to PAO resulted in diminishing ERG amplitudes in a dose-dependent manner, indicating severe retinal damage. The current study established a prototype mouse model of arsenical-induced ocular damage that can be widely used to identify the key cellular signaling pathways involved in retinal damage pathobiology and to validate medical countermeasures against the progression of ocular damage.

Therapeutic Potential of d-MAPPS™ for Ocular Inflammatory Diseases and Regeneration of Injured Corneal and Retinal Tissue.

The invasion of microbial pathogens and/or sterile inflammation caused by physical/chemical injuries, increased ocular pressure, oxidative stress, and ischemia could lead to the generation of detrimental immune responses in the eyes, which result in excessive tissue injury and vision loss. The bioavailability of eye drops that are enriched with immunoregulatory and trophic factors which may concurrently suppress intraocular inflammation and promote tissue repair and regeneration is generally low. We recently developed "derived- Multiple Allogeneic Proteins Paracrine Signaling regenerative biologics platform technology d-MAPPS™", a bioengineered biological product which is enriched with immunomodulatory and trophic factors that can efficiently suppress detrimental immune responses in the eye and promote the repair and regeneration of injured corneal and retinal tissues. The results obtained in preclinical and clinical studies showed that d-MAPPS™ increased the viability of injured corneal cells, inhibited the production of inflammatory cytokines in immune cells, alleviated inflammation, and restored vision loss in patients suffering from meibomian gland dysfunction and dry eye disease. Herewith, we emphasized molecular mechanisms responsible for the therapeutic efficacy of d-MAPPS™ and we presented the main beneficial effects of d-MAPPS™ in clinical settings, indicating that the topical administration of d-MAPPS™ could be considered a new therapeutic approach for the treatment of ocular inflammatory diseases and for the repair and regeneration of injured corneal and retinal tissues.

Bridging a Century-Old Problem: The Pathophysiology and Molecular Mechanisms of HA Filler-Induced Vascular Occlusion (FIVO)-Implications for Therapeutic Interventions.

Biocompatible hyaluronic acid (HA, hyaluronan) gel implants have altered the therapeutic landscape of surgery and medicine, fostering an array of innovative products that include viscosurgical aids, synovial supplements, and drug-eluting nanomaterials. However, it is perhaps the explosive growth in the cosmetic applications of injectable dermal fillers that has captured the brightest spotlight, emerging as the dominant modality in plastic surgery and aesthetic medicine. The popularity surge with which injectable HA fillers have risen to in vogue status has also brought a concomitant increase in the incidence of once-rare iatrogenic vaso-occlusive injuries ranging from disfiguring facial skin necrosis to disabling neuro-ophthalmological sequelae. As our understanding of the pathophysiology of these injuries has evolved, supplemented by more than a century of astute observations, the formulation of novel therapeutic and preventative strategies has permitted the amelioration of this burdensome complication. In this special issue article, we review the relevant mechanisms underlying HA filler-induced vascular occlusion (FIVO), with particular emphasis on the rheo-mechanical aspects of vascular blockade; the thromboembolic potential of HA mixtures; and the tissue-specific ischemic susceptibility of microvascular networks, which leads to underperfusion, hypoxia, and ultimate injury. In addition, recent therapeutic advances and novel considerations on the prevention and management of muco-cutaneous and neuro-ophthalmological complications are examined.

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.

A smartphone based method for mouse fundus imaging.

Noninvasive in vivo imaging of the mouse retina is essential for eye research. However, imaging the mouse fundus is challenging due to its small size and requires specialized equipment, maintenance, and training. These issues hinder the routine evaluation of the mouse retina. In this study, we developed a noncontact imaging system consisting of a smartphone, a 90D condensing lens, a homemade light diaphragm, a tripod, and a Bluetooth remote. With minimal training, examiners were able to capture fundus images from the mouse retina. We also found that fundus images captured using our system from wild type mice, mice with laser-induced retinal injury, and a mouse model of retinitis pigmentosa showed a quality similar to those captured using a commercial fundus camera. These images enabled us to identify normal structures and pathological changes in the mouse retina. Additionally, fluorescein angiography was possible with the smartphone system. We believe that the smartphone imaging system is low cost, simple, accessible, easy to operate, and suitable for the routine screening and examination of the mouse eye.

Transplanted embryonic retinal stem cells have the potential to repair the injured retina in mice.

BACKGROUND: Stem cell transplantation has been reported as one of the promising strategies to treat retinal degenerative diseases. But, the application and the role of retina stem cells (RSCs) in the treatment of patients with retinal degenerative diseases have not been fully revealed. This study aimed to investigate the potential role of transplantation of the embryo-derived RSCs into the vitreous cavity in repairing the damaged retina in mice. METHODS: RSCs were isolated from Kunming mice E17 embryonic retina and ciliary body tissues, and labeled with 5-bromo-2'-deoxyuridin (BrdU). Retinal optic nerve crush injury was induced in left eyes in male Kunming mice by ring clamping the optic nerve. The 6th -generation of BrdU-labeled RSCs were transplanted into the damaged retina by the intravitreal injection, and saline injected eyes were used as the control. Hematoxylin and eosin histological staining, and BrdU, Nestin and Pax6 immunostaining were performed. Electroretinogram (ERG) was used for assessing the electrical activity of the retina. RESULTS: Embryo-derived RSCs were identified by the positive stains of Pax6 and Nestin. BrdU incorporation was detected in the majority of RSCs. The damaged retina showed cellular nuclear disintegration and fragmentation in the retinal tissue which progressed over the periods of clamping time, and decreased amplitudes of a and b waves in ERG. In the damaged retina with RSCs transplantation, the positive staining for BrdU, Pax6 and Nestin were revealed on the retinal surface. Notably, RSCs migrated into the retinal ganglion cell layer and inner nuclear. Transplanted RSCs significantly elevated the amplitudes of a waves in retina injured eyes. CONCLUSIONS: Embryonic RSCs have similar characteristics to neural stem cells. Transplantation of RSCs by intravitreal injection would be able to repair the damaged retina.

Clozapine Worsens Glucose Intolerance, Nonalcoholic Fatty Liver Disease, Kidney Damage, and Retinal Injury and Increases Renal Reactive Oxygen Species Production and Chromium Loss in Obese Mice.

Clozapine is widely employed in the treatment of schizophrenia. Compared with that of atypical first-generation antipsychotics, atypical second-generation antipsychotics such as clozapine have less severe side effects and may positively affect obesity and blood glucose level. However, no systematic study of clozapine's adverse metabolic effects-such as changes in kidney and liver function, body weight, glucose and triglyceride levels, and retinopathy-was conducted. This research investigated how clozapine affects weight, the bodily distribution of chromium, liver damage, fatty liver scores, glucose homeostasis, renal impairment, and retinopathy in mice fed a high fat diet (HFD). We discovered that obese mice treated with clozapine gained more weight and had greater kidney, liver, and retroperitoneal and epididymal fat pad masses; higher daily food efficiency; higher serum or hepatic triglyceride, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine levels; and higher hepatic lipid regulation marker expression than did the HFD-fed control mice. Furthermore, the clozapine group mice exhibited insulin resistance, poorer insulin sensitivity, greater glucose intolerance, and less Akt phosphorylation; their GLUT4 expression was lower, they had renal damage, more reactive oxygen species, and IL-1 expression, and, finally, their levels of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and catalase) were lower. Moreover, clozapine reduced the thickness of retinal cell layers and increased iNOS and NF-κB expression; a net negative chromium balance occurred because more chromium was excreted through urine, and this influenced chromium mobilization, which did not help overcome the hyperglycemia. Our clozapine group had considerably higher fatty liver scores, which was supported by the findings of lowered adiponectin protein levels and increased FASN protein, PNPLA3 protein, FABP4 mRNA, and SREBP1 mRNA levels. We conclude that clozapine can worsen nonalcoholic fatty liver disease, diabetes, and kidney and retinal injury. Therefore, long-term administration of clozapine warrants higher attention.

Plasma Rich in Growth Factors Enhances Cell Survival after in Situ Retinal Degeneration.

PURPOSE: The purpose of this study was to examine the effect of plasma rich in growth factors (PRGFs) under blue light conditions in an in vivo model of retinal degeneration. METHODS: Male Wistar rats were exposed to dark/blue light conditions for 9 days. On day 7, right eyes were injected with saline and left eyes with PRGF. Electroretinography (ERG) and intraocular pressure (IoP) measurements were performed before and after the experiment. After sacrifice, retinal samples were collected. Hematoxylin and eosin staining was performed to analyze the structure of retinal sections. Immunofluorescence for brain-specific homeobox/POU domain protein 3A (Brn3a), choline acetyltransferase (ChAT), rhodopsin, heme oxygenase-1 (HO-1), and glial fibrillary acidic protein (GFAP) was performed to study the retinal conditions. RESULTS: Retinal signaling measured by ERG was reduced by blue light and recovered with PRGF; however, IoP measurements did not show significant differences among treatments. Blue light reduced the expression for Brn3a, ChAT, and rhodopsin. Treatment with PRGF showed a recovery in their expressions. HO-1 and GFAP results showed that blue light increased their expression but the use of PRGF reduced the effect of light. CONCLUSIONS: Blue light causes retinal degeneration. PRGF mitigated the injury, restoring the functionality of these cells and maintaining the tissue integrity.

Elevated intraocular pressure causes cellular and molecular retinal injuries, advocating a more moderate intraocular pressure setting during phacoemulsification surgery.

PURPOSE: To evaluate the cellular and molecular retinal injuries induced by various intraocular pressure (IOP) settings in a mouse model of acute ocular hypertension (AOH), and to advise using a more moderate target IOP during phacoemulsification (phaco) surgery. METHODS: A mouse model of AOH that mimics a transient IOP elevation during phacoemulsification cataract surgery was established. Six groups with various settings of target IOP were included. Retinal tissues were assessed with terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end-labeling (TUNEL) staining for neuron loss, immunofluorescence with Iba1 for microglia activation, and quantitative real-time polymerase chain reaction analysis with tight junction proteins (claudin-3 and claudin-5) or classic inflammation markers (IL-1ß and eNOS) for impairment of the blood-retinal barrier (BRB) and inflammatory injury. RESULTS: Compared with those in the 45-mmHg IOP group, significantly increased number of neurons loss and increased microglia activation were observed in 90-mmHg IOP group. In addition, the expression of claudin-3 and claudin-5 was significantly decreased, while the expression of IL1-ß and eNOS was up-regulated, indicating impairment of the BRB and inflammatory injury in the retina. Furthermore, these findings of neuron loss, microglia activation, and inflammation in the 90-mmHg groups were exacerbated when an IOP-induced retinal injury was established 5 days earlier, while those in the 45-mmHg groups remained almost unchanged. CONCLUSIONS: In conclusion, these results showed that a relatively commonly used high IOP setting (90 mmHg) could induce significantly more serious retinal injury. An IOP setting around 45 mmHg is relatively safe and might be recommended in phaco surgery, especially in patients with advanced glaucoma, previous acute angle closure crisis, or other diseases with fragile retina and optic nerve.

Glycyrrhizin protects against sodium iodate-induced RPE and retinal injury though activation of AKT and Nrf2/HO-1 pathway.

Glycyrrhizin is a bioactive triterpenoid saponin extracted from a traditional Chinese medicinal herb, glycyrrhiza, and has been reported to protect the organs such as liver and heart from injuries. However, there is no report about the effects of glycyrrhizin on atrophic age-related macular degeneration (AMD). This study investigated the effects of glycyrrhizin on retinal pigment epithelium (RPE) in vitro and retina of mice in vivo treated with sodium iodate (SI). Glycyrrhizin significantly inhibited SI-induced reactive oxygen species (ROS), and decreased apoptosis of RPE in vitro. The underlying mechanisms included increased phosphorylation of Akt, and increased expression of nuclear factor erythroid 2-related factor2 (Nrf-2) and HO-1, thereby protecting RPE from SI-induced ROS and apoptosis. Furthermore, glycyrrhizin significantly decreased the apoptosis of retinal cells in vivo, resulting in the inhibition of thinning of retina, decreasing the number of drusen and improving the function of retina. These findings suggested that glycyrrhizin may be a potential candidate for the treatment of atrophic AMD in clinical practice.

The effects of lutein on cisplatin-induced retinal injury: an experimental study.

AIM: Lutein is one of the most common carotenoids defined in human plasma as having potent anti-oxidant effects. We aimed to determine the biochemical and histopathological effects of lutein on cisplatin-induced oxidative retinal injury in rats. MATERIALS AND METHODS: Twenty-four rats were equally divided into four groups as healthy controls (HC group), only cisplatin (5 mg/kg) administered group (CIS group), Lutein (0.5 mg/kg) + cisplatin (5 mg/kg) administered group (LC group), and only Lutein (0.5 mg/kg) (LUT group) administered group. From the blood samples obtained, serum malondialdehyde (MDA), total glutathione (tGSH), interleukin 1 beta (IL-1ß), and tumor necrosis factor alpha (TNF-α) levels were investigated. In histopathological analyses, the total retinal thickness, retinal pigment epithelium (RPE), photoreceptor layer (PL), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL) were evaluated. RESULTS: MDA, IL-1ß, and TNF-a levels were statistically significantly higher (p < 0.001) in CIS group compared with other three groups while tGSH levels were statistically significantly lower (p < 0.001). In subgroup analyses, there was no any statistically significant difference regarding all four parameters analyzed between HC, LC, and LUT groups. In histopathological analyses, cisplatin-induced retinal damage included atrophy and disorganization on outer segment, degeneration and detachment of RPE and PL from choroid, degeneration and edema of INL and IPL, total degeneration of GCL; while cisplatin-induced retinal damage was determined to be significantly prevented with 0.5 mg lutein treatment on histopathological evaluations. CONCLUSIONS: Lutein co-administration was highly effective in prevention of cisplatin-induced retinal damage due to the anti-oxidant and anti-inflammatory effects of lutein.

Effect of human umbilical cord blood mesenchymal stem cells administered by intravenous or intravitreal routes on cryo-induced retinal injury.

Traumatic optic neuropathy is an important cause of severe vision loss. So, many attempts were performed to transplant stem cells systemically or locally to regenerate the injured retina. In this study, we investigated the effect of human umbilical cord blood mesenchymal stem cells (hUBMSCs) on histological structure, apoptotic, antiapoptotic, oxidant and antioxidant markers in an experimental model of cryo-induced retinal damage in mice. Forty-eight mice were included with 4 major groups; group I contained 18 mice as controls. The others included 30 mice exposed to cryo-induced retinal injury and were subdivided into three equal groups: group II received no treatment after injury. Group III was intravenously injected with hUCBMSCs after injury and group IV received an intravitreal injection with hUCBMSCs into both eyes. Retinal tissues were used for histopathological, immunological and gene expression studies. Real time-PCR was performed to assess B-cell lymphoma 2 (bcl2), Bcl2-associated X protein (bax), heme oxygenase-1 (hmox-1) and thioredoxin-2 (tnx-2) expression and to assess the differentiation of the stem cells into the retinal tissue. Immunohistochemical analysis was performed to assess caspase-3, 3-nitrotyrosine (3-NT) and basic fibroblast growth factor (bFGF). Disturbed retinal structure was seen in cryo-injured mice while hUCBMSCs treated groups showed nearly normal structure. By real time-PCR, significantly reduced mRNA expressions of Bax and notably enhanced mRNA expression of Bcl-2, hmox-1 and txn-2 were demonstrated in retinal injured mice with hUCBMSCs treatment compared to those without. In addition, immunohistochemical analysis confirmed downregulation of 3-NT and caspase-3 and upregulation of bFGF after hUCBMSCs injection in injured retina. Furthermore, there was no differentiation of transplanted stem cells into the retinal tissue. In conclusions, hUCBMSCs could improve the morphological retinal structure in cryo-induced retinal damage model by modulation of the oxidant-apoptotic status and by increased the expression of bFGF. © 2017 IUBMB Life, 69(3):188-201, 2017.

Femtosecond Laser Eyewear Protection: Measurements and Precautions.

Ultrafast laser systems are becoming more widespread throughout the research and industrial communities yet eye protection for these high power, bright pulsed sources still require scrupulous characterization and testing before use. Femtosecond lasers, with pulses naturally possessing broad-bandwidth and high average power with variable repetition rate, can exhibit spectral side-bands and subtly changing center wavelengths, which may unknowingly affect eyewear safety protection. Pulse spectral characterization and power diagnostics are presented for a 80 MHz, Ti+3:Sapphire, ≈ 800 nm, ≈40 femtosecond oscillator system. Power and spectral transmission for 22 test samples are measured to determine whether they fall within manufacturer specifications.

Deferasirox nanosuspension loaded dissolving microneedles for ocular drug delivery.

Deferasirox (DFS) is an oral iron chelator that is employed in retinal ailments as a neuroprotectant against retinal injury and thus has utility in treating disorders such as excitoneurotoxicity and age-related macular degeneration (AMD). However, the conventional oral route of administration can present several disadvantages, e.g., the need for more frequent dosing and the first-pass effect. Microneedles (MNs) are minimally invasive systems that can be employed for intrascleral drug delivery without pain and can advantageously replace intravitreal injections therapy (IVT) as well as conventional oral routes of delivery for DFS. In this study, DFS was formulated into a nanosuspension (NS) through wet media milling employing PVA as a stabilizer, which was successfully loaded into polymeric dissolving MNs. DFS exhibited a 4-fold increase in solubility in DFS-NS compared to that of pure DFS. Moreover, the DFS-NSs exhibited excellent short-term stability and enhanced thermal stability, as confirmed through thermogravimetric analysis (TGA) studies. The mechanical characterization of the DFS-NS loaded ocular microneedles (DFS-NS-OcMNs), revealed that the system was sufficiently strong for effective scleral penetration. Optical coherence tomography (OCT) images confirmed the insertion of 81.23 ± 7.35 % of the total height of the MN arrays into full-thickness porcine sclera. Scleral deposition studies revealed 64 % drug deposition after just 5 min of insertion from DFS-NS-loaded ocular microneedles (OcMNs), which was almost 5 times greater than the deposition from pure DFS-OcMNs. Furthermore, both DFS and DFS-NS-OcMN exhibited remarkable cell viability when evaluated on human retinal pigment (ARPE) cells, suggesting their safety and appropriateness for use in the human eye. Therefore, loading DFS-NS into novel MN devices is a promising technique for effectively delivering DFS to the posterior segment of the eye in a minimally invasive manner.

Role of monocarboxylate transporters in AMPK-mediated protection against excitotoxic injury in the rat retina.

Activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway protects against N-methyl-D-aspartic acid (NMDA)-induced excitotoxic retinal injury. AMPK activation enhances fatty acid metabolism and ketone body synthesis. Ketone bodies are transported into neurons by monocarboxylate transporters (MCTs) and exert neuroprotective effects. In this study, we examined the distribution and expression levels of MCT1 and MCT2 in the retina and analyzed the effects of pharmacological inhibition of MCTs on the protective effects of metformin and 5-aminoimidazole-4-carboxamide (AICAR), activators of AMPK, against NMDA-induced retinal injury in rats. MCT1 was expressed in the blood vessels, processes of astrocytes and Müller cells, and inner segments of photoreceptors in the rat retina, whereas MCT2 was expressed in neuronal cells in the ganglion cell layer (GCL) and in astrocyte processes. The expression levels of MCT2, but not MCT1, decreased one day after intravitreal injection of NMDA (200 nmol). Intravitreal injection of NMDA decreased the number of cells in the GCL compared to the vehicle seven days after injection. Simultaneous injection of metformin (20 nmol) or AICAR (50 nmol) with NMDA attenuated NMDA-induced cell loss in the GCL, and these protective effects were attenuated by AR-C155858 (1 pmol), an inhibitor of MCTs. AR-C155858 alone had no significant effect on the retinal structure. These results suggest that AMPK-activating compounds protect against NMDA-induced excitotoxic retinal injury via mechanisms involving MCTs in rats. NMDA-induced neurotoxicity may be associated with retinal neurodegenerative changes in glaucoma and diabetic retinopathy. Therefore, AMPK-activating compounds may be effective in managing these retinal diseases.

Impaired pericyte-Müller glia interaction via PDGFRß suppression aggravates photoreceptor loss in a rodent model of light-induced retinal injury.

AIM: To investigate the involvement of pericyte-Müller glia interaction in retinal damage repair and assess the influence of suppressing the platelet-derived growth factor receptor ß (PDGFRß) signaling pathway in retinal pericytes on photoreceptor loss and Müller glial response. METHODS: Sprague-Dawley rats were exposed to intense light to induce retinal injury. Neutralizing antibody against PDGFRß were deployed to block the signaling pathway in retinal pericytes through intravitreal injection. Retinal histology and Müller glial reaction were assessed following light injury. In vitro, normal and PDGFRß-blocked retinal pericytes were cocultured with Müller cell line (rMC-1) to examine morphological and protein expression changes upon supplementation with light-injured supernatants of homogenized retinas (SHRs). RESULTS: PDGFRß blockage 24h prior to intense light exposure resulted in a significant exacerbation of photoreceptor loss. The upregulation of GFAP and p-STAT3, observed after intense light exposure, was significantly inhibited in the PDGFRß blockage group. Further upregulation of cytokines monocyte chemoattractant protein 1 (MCP-1) and interleukin-1ß (IL-1ß) was also observed following PDGFRß inhibition. In the in vitro coculture system, the addition of light-injured SHRs induced pericyte deformation and upregulation of proliferating cell nuclear antigen (PCNA) expression, while Müller cells exhibited neuron-like morphology and expressed Nestin. However, PDGFRß blockage in retinal pericytes abolished these cellular responses to light-induced damage, consistent with the in vivo PDGFRß blockage findings. CONCLUSION: Pericyte-Müller glia interaction plays a potential role in the endogenous repair process of retinal injury. Impairment of this interaction exacerbates photoreceptor degeneration in light-induced retinal injury.

An Update to Biomechanical and Biochemical Principles of Retinal Injury in Child Abuse.

Abusive head trauma (AHT) is an extreme form of physical child abuse, a subset of which is shaken baby syndrome (SBS). While traumatic injury in children is most readily observed as marks of contusion on the body, AHT/SBS may result in internal injuries that can put the life of the child in danger. One pivotal sign associated with AHT/SBS that cannot be spotted with the naked eye is retinal injury (RI), an early sign of which is retinal hemorrhage (RH) in cases with rupture of the retinal vasculature. If not addressed, RI can lead to irreversible outcomes, such as visual loss. It is widely assumed that the major cause of RI is acceleration-deceleration forces that are repeatedly imposed on the patient during abusive shaking. Still, due to the controversial nature of this type of injury, few investigations have ever sought to delve into its biomechanical and/or biochemical features using realistic models. As such, our knowledge regarding AHT-/SBS-induced RI is significantly lacking. In this mini-review, we aim to provide an up-to-date account of the traumatology of AHT-/SBS-induced RI, as well as its biomechanical and biochemical features, while focusing on some of the experimental models that have been developed in recent years for studying retinal hemorrhage in the context of AHT/SBS.

Non-postoperative Central Retinal Artery and Ophthalmic Artery Occlusion With Compression Ischemia Due to Prolonged Sedation In Prone Position.

Central retinal artery occlusion (CRAO) after a prolonged period of lying prone is a rare condition with only a handful of cases reported, generally as a postoperative complication of spinal surgery. Only a few cases can be found describing acute visual loss following intravenous drug abuse and stupor leading to continuous pressure on the orbit while asleep. No cases can be found describing acute visual loss following the ingestion of oral sedating/antipsychotic medications. Urgent identification and workup with subsequent interventions are needed to offer the highest probability of full/partial visual restoration. Our patient presented with complete vision loss after ingesting oral antipsychotic medications leading to a prolonged sedated state in which compressive ischemia led to central retinal artery occlusion. The complex timeline regarding the patient's presentation and the implications relating to offered interventions are highlighted in this case report.

Necroptosis plays a crucial role in the exacerbation of retinal injury after blunt ocular trauma.

Retinal injury after blunt ocular trauma may directly affect prognosis and lead to vision loss. To investigate the pathological changes and molecular mechanisms involved in retinal injury after blunt ocular trauma, we established a weight drop injury model of blunt ocular trauma in male Beagle dogs. Hematoxylin-eosin staining, immunofluorescence staining, western blotting, and TUNEL assays were performed to investigate retinal injury within 14 days after blunt ocular trauma. Compared with the control group, the thicknesses of the inner and outer nuclear layers, as well as the number of retinal ganglion cells, gradually decreased within 14 days after injury. The number of bipolar cells in the inner nuclear layer began to decrease 1 day after injury, while the numbers of cholinergic and amacrine cells in the inner nuclear layer did not decrease until 7 days after injury. Moreover, retinal cell necroptosis increased with time after injury; it progressed from the ganglion cell layer to the outer nuclear layer. Visual electrophysiological findings indicated that visual impairment began on the first day after injury and worsened over time. Additionally, blunt ocular trauma induced nerve regeneration and Müller glial hyperplasia; it also resulted in the recruitment of microglia to the retina and polarization of those microglia to the M1 phenotype. These findings suggest that necroptosis plays an important role in exacerbating retinal injury after blunt ocular trauma via gliosis and neuroinflammation. Such a role has important implications for the development of therapeutic strategies.