Considerations for the Use of Photobiomodulation in the Treatment of Retinal Diseases.

Photobiomodulation (PBM) refers to the beneficial effect produced from low-energy light irradiation on target cells or tissues. Increasing evidence in the literature suggests that PBM plays a positive role in the treatment of retinal diseases. However, there is great variation in the light sources and illumination parameters used in different studies, resulting in significantly different conclusions regarding PBM's therapeutic effects. In addition, the mechanism by which PBM improves retinal function has not been fully elucidated. In this study, we conducted a narrative review of the published literature on PBM for treating retinal diseases and summarized the key illumination parameters used in PBM. Furthermore, we explored the potential molecular mechanisms of PBM at the retinal cellular level with the goal of providing evidence for the improved utilization of PBM in the treatment of retinal diseases.

Orbital and eyelid diseases: The next breakthrough in artificial intelligence?

Orbital and eyelid disorders affect normal visual functions and facial appearance, and precise oculoplastic and reconstructive surgeries are crucial. Artificial intelligence (AI) network models exhibit a remarkable ability to analyze large sets of medical images to locate lesions. Currently, AI-based technology can automatically diagnose and grade orbital and eyelid diseases, such as thyroid-associated ophthalmopathy (TAO), as well as measure eyelid morphological parameters based on external ocular photographs to assist surgical strategies. The various types of imaging data for orbital and eyelid diseases provide a large amount of training data for network models, which might be the next breakthrough in AI-related research. This paper retrospectively summarizes different imaging data aspects addressed in AI-related research on orbital and eyelid diseases, and discusses the advantages and limitations of this research field.

Suppressing endoplasmic reticulum stress-related autophagy attenuates retinal light injury.

Excessive light exposure is a principal environmental factor, which can cause damage to photoreceptors and retinal pigment epithelium (RPE) cells and may accelerate the progression of age-related macular degeneration (AMD). In this study, oxidative stress, endoplasmic reticulum (ER) stress and autophagy caused by light exposure were evaluated in vitro and in vivo. Light exposure caused severe photo-oxidative stress and ER stress in photoreceptors (661W cells) and RPE cells (ARPE-19 cells). Suppressing either oxidative stress or ER stress was protective against light damage in 661W and ARPE-19 cells and N-acetyl-L-cysteine treatment markedly inhibited the activation of ER stress caused by light exposure. Moreover, suppressing autophagy with 3-methyladenine significantly attenuated light-induced cell death. Additionally, inhibiting ER stress either by knocking down PERK signals or with GSK2606414 treatment remarkably suppressed prolonged autophagy and protected the cells against light injury. In vivo experiments verified neuroprotection via inhibiting ER stress-related autophagy in light-damaged retinas of mice. In conclusion, the above results suggest that light-induced photo-oxidative stress may trigger subsequent activation of ER stress and prolonged autophagy in photoreceptors and RPE cells. Suppressing ER stress may abrogate over-activated autophagy and protect the retina against light injury.

Elevated lymphocyte specific protein 1 expression is involved in the regulation of leukocyte migration and immunosuppressive microenvironment in glioblastoma.

Immune cell infiltration mediates therapeutic response to immune therapies. The investigation on the genes regulating leukocyte migration may help us to understand the mechanisms regulating immune cell infiltration in tumor microenvironment. Here, we collected the data from Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) to analyze the expression of leukocyte migration related genes in glioblastoma (GBM). Lymphocyte specific protein 1 (LSP1) was identified as the only gene in this family which not only has an elevated expression, but also serve as an independent predictive factor for progressive malignancy in glioma. We further confirmed these results in clinical glioma samples by quantitative PCR, immunofluorescence, immunohistochemistry, and western blot. Moreover, LSP1 expression was closely related to the response to radio- and chemotherapy in GBM, and positively correlated with immunosuppressive cell populations, including M2 macrophages, neutrophil, and regulatory T cell. Additionally, elevated LSP-1 expression enhanced the expression of immunosuppression related genes like programmed cell death 1 (PD1) and leukocyte associated immunoglobulin like receptor 1 (LAIR1) in macrophages. LSP1 also promoted the migration of macrophages. Together, our study suggests a novel role of LSP1 contributing to immunosuppressive microenvironment in GBM and serving as a potential therapeutic target for it.

Analysis from the perspective of cilia: the protective effect of PARP inhibitors on visual function during light-induced damage.

PURPOSE: To analyze the protective effect of PARP inhibitors on light-damaged retina and explore its possible mechanism from the perspective of ciliopathy. METHODS: A systematic review of the literature was performed to investigate the protection of PARP inhibition on light-damaged cilia. PubMed database was retrieved to find the relevant studies and 119 literatures were involved in the review. RESULTS: In retina, the outer segment of photoreceptor is regarded as a special type of primary cilium, so various retinal diseases actually belong to a type of ciliopathy. The retina is the only central nervous tissue exposed to light, but poly (ADP-ribose) polymerase (PARP), as a nuclear enzyme repairing DNA breaks, is overactivated during the light-induced DNA damage, and is involved in the cell death cascade. Studies show that both ATR and phosphorylated Akt colocalize with cilium and play an important role in regulating ciliary function. PARP may function at ATR or PI3K/Akt signal to exert protective effect on cilia. CONCLUSION: PARP inhibitors may protect the cilia/OS of photoreceptor during light-induced damage, which the possible mechanism may be involved in the activation of ATR and PI3K/Akt signal.

Entrapment of the temporal horn secondary to postoperative gamma-knife radiosurgery in intraventricular meningioma: A case report.

BACKGROUND: Entrapment of the temporal horn (ETH) is a rare pathologic condition. It is a kind of focal hydrocephalus caused by obstruction of flow pathway of cerebrospinal fluid. It is caused by various conditions, but ETH secondary to postoperative gamma-knife radiosurgery (GKS) is extremely rare. CASE SUMMARY: A 52-year old previously healthy woman underwent resection of a large intraventricular meningioma. A small fragment of residual tumor with no obvious enlargement of the temporal horn was observed 3 mo after surgery, and she was referred for GKS. Two months after GKS, she complained of headache and progressive paralysis of the left limb. Magnetic resonance imaging revealed enlargement of the temporal horn. There was a second procedure to resect the residual tumor 8 mo after GKS. After the second procedure, she recovered smoothly. As of the date of this writing, she has remained in good condition. CONCLUSION: This case reminds us that ETH should be considered in the treatment of intraventricular meningiomas, especially before GKS.

Therapeutic hypothermia protects photoreceptors through activating Cirbp pathway.

Therapeutic hypothermia as a physical method to lower the brain temperature of patients has been widely used in clinics as an effective and necessary step during the treatment of acute brain injury or edema. However, due to limitations of the ocular structure, the application of hypothermia in retinal neuroprotection still has an obvious barrier. Here, the neuroprotective mechanism produced by hypothermia in the retina was investigated, with the hopes of deciphering the key molecular targets of the signaling pathway to finally realize the ocular neuroprotection by regulating specific molecular targets. In present study, it was first demonstrated that hypothermia produced significant neuroprotection on photoreceptors (661 W cell) against glucose deprivation (GD)-induced injury in vitro and visible light-induced retinal damage in vivo. The results disclosed that hypothermia (32 °C) was able to attenuate the upregulation of heme oxygenase-1, cleaved Caspase-3, cleaved Caspase-9, and B-cell lymphoma-2-associated X caused by GD, and restored the decline of protective factor B-cell lymphoma-2 as well. Moreover, hypothermia suppressed the excessive generation of intracellular reactive oxygen species and depolarization of mitochondrial membrane potential, and showed marked neuroprotection against GD-induced damage in photoreceptors, which significantly reduced cell death percentage in vitro. In in vivo experiments, it was found that hypothermia was able to protect retinal function against light injury, restoring the decline of a-waves and b-waves in electroretinograms and maintaining the thickness of the retinal outer nuclear layer. Furthermore, hypothermia blocked the visible light-induced cell death pathway in the retina, suppressing poly(ADP-ribose) polymerase-1 activation. More importantly, it was demonstrated that cold-inducible RNA-binding protein (Cirbp) as a key molecular target played an important role in hypothermia-induced neuroprotection, which is the first proof of its function in ophthalmology. In in vitro experiments, hypothermia caused marked expression of Cirbp in photoreceptors. And reducing the expression of Cirbp with specific small interfering RNA was able to block the hypothermia-induced neuroprotection. Consistently, overexpressed Cirbp with Cirbp-gene-modified lentivirus mimicked the neuroprotection against GD-induced injury even under normal temperature (37 °C) conditions. Additionally, the overexpression of Cirbp was detected in hypothermia-treated retinas. These results indicate that hypothermia promotes neuroprotection in photoreceptors via activation of the Cirbp pathway. The study presented here suggests that therapeutic hypothermia may promote neuroprotection in the retina by activating Cirbp, and regulating Cirbp may mimic similar protection even under normal temperature conditions, which might be a specific molecular target in retinal neuroprotection.

Case report: an intriguing sign in a patient with an inferior rectus muscle granular cell tumor.

RATIONALE: Occurrence of granulosa cell tumors (GCTs) in the eye are rare and may be diagnosed by imaging examination and immune-histochemical studies. Two common signs of a rectus muscle tumor are the proptosis of the eye ball and the complaint of bi-ocular diploma. PATIENT CONCERNS: A 45-year-old man visited our ophthalmology department with an about a 3-year history of vertical diplopia. His visual acuity when looking forward was normal but was severely low when gazing upward. DIAGNOSIS: Histopathological analysis demonstrated that the encapsulated tumor contained large nested or cord-like cells with small nuclei and abundant eosinophilic cytoplasmic particles. Immunohistochemistry showed that tumor cells strongly expressed CD68, S100 and vimentin, were weakly positive for Ki67, and negative for CK. The tumor was diagnosed as a GCT. INTERVENTIONS: The tumor was surgically removed via a transconjunctival approach along inferior rectus muscle. OUTCOMES: The severe loss of acuity when gazing upward was ameliorated after surgery, but global mobility did not improve. Long-term follow-up was still needed. LESSONS: Ophthalmologists should be aware that when a patient's visual acuity is normal when looking forward but severely low when gazing upward, it may be a sign of a GCT of the inferior rectus muscle.

Resveratrol protects photoreceptors by blocking caspase- and PARP-dependent cell death pathways.

Retinal degeneration is a major cause of severe vision loss and irreversible blindness and is characterized by progressive damage to retinal photoreceptor cells. Resveratrol (RSV) serves as an activator of the histone deacetylase, Sirt1, and has been shown to exert anti-oxidative properties. In this study, we mimicked retinal degeneration by subjecting photoreceptors (661 W cells) to glucose deprivation (GD) or light exposure. Under these conditions, we investigated the mechanisms underlying GD- or light exposure-induced cell death and the protective effect of RSV. We found that GD and light exposure resulted in mitochondrial dysfunction, oxidative stress, and cell death. Treatment of injured cells with RSV decreased the production of reactive oxygen species (ROS), improved the ratio of reduced/oxidized glutathione (GSH/GSSG), mitochondrial membrane potential and morphology, and reduced apoptosis. We used the caspase inhibitor, z-VAD-fmk, and a lentiviral-mediated shRNA knockdown of PARP-1 to reveal that GD and light exposure-induced cell death have different underlying mechanisms; GD triggered a caspase-dependent cell death pathway, whereas light exposure triggered a PARP-dependent cell death pathway. The level of caspase-9 and caspase-3, upregulated following GD, were reduced by treatment with RSV. Similarly, the level of PARP-1 and AIF, upregulated following light exposure, were decreased by treatment with RSV. Additionally, treatment with RSV elevated the protein expression and enzymatic activity of Sirt1 and a Sirt1 inhibitor reduced the protective effect of RSV against insult-induced cellular injuries, indicating that RSV's protective effect may involve Sirt1 activation. Finally, we investigated the neuroprotection of RSV in vivo. Administration of RSV to mice under extreme light exposure led to a suppression of the light-induced thinning of the outer nuclear layer (ONL) detected by hematoxylin and eosin (H&E) staining and restored retinal function evaluated by electroretinography (ERG). Taken together, our findings provide evidence that treatment with RSV has neuroprotective effects on both GD and light exposure-induced cell death pathways in photoreceptor cells.

Antiapoptotic role of the cellular repressor of E1A-stimulated genes (CREG) in retinal photoreceptor cells in a rat model of light-induced retinal injury.

OBJECTIVE: Light injury-induced apoptosis of retinal photoreceptor cells can lead to vision loss. The mechanism underlying such injury remains unclear, and there are no effective therapies at present. The aim of this study was to examine the potential antiapoptotic role of the cellular repressor of E1A-stimulated genes (CREG) in retinal cells in a rat model of light-induced retinal damage. METHODS: CREG proteins were injected into the vitreous space of rats in which light retinal injury was induced. An equal volume of PBS was injected into the vitreous space of a control group. Retinas were collected for H&E staining and Western blotting analysis 1, 3, and 7 days later. Inhibitors or agonist for P38, JNK, and AKT were injected into the vitreous space to verify CREG function. RESULTS: In rats with light-induced retinal injury, the CREG treatment inhibited the expression of apoptosis-related proteins caspase-3, caspase-8, and caspase-9 and signaling proteins phosphorylated ERK (P-ERK), phosphorylated JNK (P-JNK), phosphorylated P38 (P-P38), and phosphorylated AKT (P-AKT). An inhibitor of PI3K-AKT and an agonists of P38 and JNK abrogated the inhibitory effect of CREG on caspase-3 expression. CONCLUSION: CREG protected retinal cells against apoptosis by inhibiting P38/MAPK and JNK/MAPK signaling pathways and activating the PI3K-AKT signaling pathway.

Potential Role of Induced Pluripotent Stem Cells as Regenerative Medicine in Retinal Cell Damage.

Induced pluripotent stem cells (also called iPSCs) are somatic cells reprogrammed by overexpressing four nuclear transcriptional factors containing Sox2, Klf4, c-myc and Oct4 is the one of research hotspots. Its pluripotency, self-renewal capacity and wide accessibility to donor tissues have made possible the means for modified regenerative medicine. They are considered a possible basis of healthy tissue to cure diseases, like ophthalmic diseases, degenerative diseases, age-related macular degeneration (AMD), are primarily because of the weakening capability of photoreceptor cells, retinal ganglion cells (RGCs), retinal pigmented epithelium (RPE) or other retinal cells. And these retinal cells are unable to regenerate and currently there are no effective treatments to restore sight. iPSCs allow for the in vitro development of numerous varieties of retinal cells, and may treat these diseases by retinal transplantation. Although other stem cells could differentiate into retinal cells, iPSCs derived retinal cells might have numerous benefits as compared to other stem cell sources including embryonic stem (ES) cells. Mainly they would be directly obtained from the patient, therefore eradicating every probable chance of adverse immune responses. Second, making iPSCs just needs somatic cells, thus circumventing the valid ethical issues which limited the clinic use of ES cells derived from human. Third, iPSCs are parallel to ES cells in differentiation ability, they can be expanded in vitro and induced to differentiate into retinal cells, providing a renewable source for therapeutic applications and scientific researches. In this current review, we have concise latest progresses.

Clinical effects of 3-D printing-assisted personalized reconstructive surgery for blowout orbital fractures.

PURPOSE: One of the key challenges during orbital fracture reconstructive surgery, due to the complex anatomy of the orbit, is shaping and trimming the precise contour of the implants. The objectives of this study were to describe and evaluate the use of a three-dimensional (3-D) printing technique for personalized reconstructive surgery for repairing orbital fractures. METHODS: A total of 29 cases which had 3-D technique-assisted surgical reconstruction, and 27 cases which had traditional surgery, were retrospectively analyzed. Preoperative and postoperative CT images were measured using MIMICS software, and the contour of the fracture zone and the Medpor-titanium implant were analyzed and compared. The surgical duration was also compared between the two groups. RESULTS: There were statistically significant differences in the maximum width, depth and area between fracture zone and implant between the two groups, with the absolute value in the 3-D group markedly lower as compared to the control group. In addition, the difference in the medial-inferior wall angle between the surgical eye and healthy eye was also statistically significant between the groups. The average surgical duration in the 3-D group was substantially shorter than in the control group. Additionally, the postoperative clinical evaluation in the 3-D group was superior to that of the control group. CONCLUSION: The 3-D printing technique is of great value for predicting the precise fracture zone before, and during, personalized surgery, and can help surgeons achieve accurate anatomical reconstruction for repairs of blowout orbital fractures. Moreover, the simulated bone template produced by 3-D printing models allows for "true-to-original" orbital reconstruction, which can shorten the surgical duration and improve the accuracy and safety of the operation.

Diterpenoids from Wedelia prostrata and Their Derivatives and Cytotoxic Activities.

One new ent-kaurane diterpenoid, 11ß,16α-dihydroxy-ent-kauran-19-oic acid (1), together with eight known analogues 2 - 9 were isolated from the aerial parts of Wedelia prostrata. One of the acidic diterpenoids, kaurenoic acid (3), was converted to seven derivatives, 10 - 16. All compounds were evaluated for their cytotoxic activity in vitro against human leukemia (K562), liver (HepG-2), and stomach (SGC-7901) cancer cell lines. Only four kaurenoic acid derivatives, 13 - 16, with 15-keto and substitutions at C(19) position, exhibited notable cytotoxic activities on these tumor cell lines with IC50 value ranging from 0.05 to 3.71 µm. Compounds 10 - 12, with oxime on C(15) showed moderate inhibitory effects and compounds 1 - 9 showed no cytotoxicities on them. Structure-activity relationships were also discussed based on the experimental data obtained. The known derivative, 15-oxokaurenoic acid 4-piperdin-1-ylbutyl ester (17), induced typical apoptotic cell death in colon SW480 cells upon evaluation of the apoptosis-inducing activity by flow-cytometric analysis.

Isolation, chemical characterization, and immunomodulatory activity of naturally acetylated hemicelluloses from bamboo shavings.

Bamboo shavings, the outer or intermediate layer of bamboo stems, are the bulk of by-products produced in bamboo processing. In this study we investigated the isolation, chemical characterization, and immunostimulatory activity in vitro of the hemicelluloses from bamboo shavings. Shavings were first pretreated by steam explosion. The optimal pretreatment was found to be steam explosion at 2.2 MPa for 1 min. Following this pretreatment, the yield of hemicelluloses reached (2.05±0.22)% (based on the dry dewaxed raw materials), which was 5.7-fold higher than that of untreated samples. Bamboo-shavings hemicellulose (BSH) was then prepared by hot water extraction and ethanol precipitation from the steam-exploded shavings. Purification of BSH by anion-exchange chromatography of diethylaminoethanol (DEAE)-sepharose Fast Flow resulted in a neutral fraction (BSH-1, purity of 95.3%, yield of 1.06%) and an acidic fraction (BSH-2, purity of 92.5%, yield of 0.79%). The weight-average molecular weights (Mw) of BSH-1 and BSH-2 were 12 800 and 11 300 g/mol, respectively. Chemical and structural analyses by Fourier transform infrared spectroscopy (FT-IR), 1D (1H and 13C) and 2D (heteronuclear single quantum correlation (HSQC)) nuclear magnetic resonance (NMR) spectra revealed that BSH-1 was O-acetylated-arabinoxylan and BSH-2 was O-acetylated-(4-O-methylglucurono)-arabinoxylan. BSH-1 had a higher content of acetyl groups than BSH-2. For the immunomodulatory activity in vitro, BSH and BSH-2 significantly stimulated mouse splenocyte proliferation while BSH-1 had no effect; BSH, BSH-1, and BSH-2 markedly enhanced the phagocytosis activity and nitric oxide production of the murine macrophage RAW264.7 in a dose-dependent manner. Our results suggest that the water-extractable hemicelluloses from steam-exploded bamboo shavings are naturally acetylated and have immunostimulatory activity.

Case report repairing orbital skin defects using composite flaps after giant eyelid-derived tumor excision and orbital exenteration.

RATIONALE: Though giant malignant tumors arising in the eyelid are rare, they often require extensive surgery for removal along with orbital exenteration. Because of this, repairing orbital defects is an important factor in the surgical strategy. PATIENT CONCERNS: Case 1 was a 78-year-old nomad man who presented in the Department of Ophthalmology with a giant tumor in his right eyelid, which had developed over three years. Clinical examination revealed a huge pigmented, nonhealing ulcerated lesion, approximately 52×44×40 mm in size. Case 2 was a 52-year old rural male complaining of a huge tumor in the right eyelid. Patient medical history revealed that the mass was initially the size of a soybean and gradually grew over 3 years to the size of a fist. DIAGNOSES: Histopathological examination of the tumors revealed that one was a basal cell carcinoma and the other a sebaceous gland carcinoma. INTERVENTIONS: The two cases of giant malignant eyelid tumors were surgically excised using rapid frozen section margin control. Different pedicle myocutaneous flaps were used to repair the orbital skin defects. OUTCOMES: Postoperative follow-up showed perfect healing of the pedicle flaps and good patient compliance. The results of these cases indicate that covering exposed orbital cavities with composite pedicle mycuaneous flaps is a simple and practical strategy for orbital reconstruction. Not only does this help maintain orbital stability, but it also provides opportunities for patients to return to normal lives. LESSONS: Although surgical management is often the first option for treatment of giant eyelid tumors, recurrence and mortality due to the tumors is still high after long-term follow-up. Therefore, early discovery and treatment is the best way to control the progression of giant eyelid tumors and enhance survivability.

Croceicoccus pelagius sp. nov. and Croceicoccus mobilis sp. nov., isolated from marine environments.

Strain Ery9T, isolated from surface seawater of the Atlantic Ocean, and strain Ery22T, isolated from deep-sea sediment of the Indian Ocean, were subjected to a taxonomic study using a polyphasic approach. Cells of the two strains were Gram-stain-negative, aerobic and rod-shaped. They produced yellow pigments and lacked bacteriochlorophyll a. On the basis of 16S rRNA gene sequence analysis, strain Ery9T was closely related to Croceicoccus naphthovorans PQ-2T (with 16S rRNA gene sequence similarity of 97.7 %), and strain Ery22T was closely related to Croceicoccusmarinus E4A9T (98.3 %). The 16S rRNA gene sequence similarity between strain Ery9T and strain Ery22T was 96.6 %. Phylogenetic analyses revealed that strains Ery9T and Ery22T fell within the cluster of the genus Croceicoccus and represented two independent lineages. The average nucleotide identity (ANI) values and the genome-to-genome distances between strains Ery9T and Ery22T and the type strains of species of the genus Croceicoccus with validly published names were 73.7-78.4 % and 20.1-22.3 %, respectively. The major respiratory quinone of the two isolates was ubiquinone-10 (Q-10). The DNA G+C contents of strains Ery9T and Ery22T were 62.8 and 62.5 mol%, respectively. Differential phylogenetic distinctiveness and chemotaxonomic differences, together with phenotypic properties, revealed that strains Ery9T and Ery22T could be differentiated from their closely related species. Therefore, it is concluded that strains Ery9T and Ery22T represent two novel species of the genus Croceicoccus, for which the names Croceicoccus pelagius sp. nov. (type strain Ery9T=CGMCC 1.15358T=DSM 101479T) and Croceicoccus mobilis sp. nov. (type strain Ery22T=CGMCC 1.15360T=DSM 101481T), are proposed.

Suppressing autophagy protects photoreceptor cells from light-induced injury.

Autophagy, a conserved cellular self-degradation process, not only serves to protect cells at critical times during development and nutrient stress, but also contributes to cell death. Photoreceptor cells are unique neurons which when directly exposed to the light, transduces light stimuli into visual signal. However, intense light exposure can be cytotoxic to the retina. So far, the precise mechanism underlying retina light injury remains unknown, and the effective therapy is still unavailable. Here, we found that visible light exposure activated the mitogen-activated protein kinases (MAPK) pathway and led to remarkable autophagy in photoreceptor cells (661W cells). Directly blocking autophagy with 3MA or LY294002 markedly attenuated light-induced death in 661W cells. Among the activated downstream factors of MAPK pathway, ERK, not JNK or p-38, played a critical role in light-induced death mechanism. Inhibiting the activation of ERK with its specific inhibitor PD98059 significantly suppressed light-induced autophagy and protected 661W cells from light injury. These results indicate that autophagy is an essential event in light-induced photoreceptor death and that directly blocking autophagy or suppressing autophagy by inhibiting the ERK pathway could effectively attenuates light-induced damage. These observations may have a potential application in the treatment of retinal light injury.

Rapamycin attenuates visible light-induced injury in retinal photoreceptor cells via inhibiting endoplasmic reticulum stress.

An extended exposure of the retina to visible light may lead to photochemical damage in retinal photoreceptor cells. The exact mechanism of retinal light damage remains unknown, and an effective therapy is still unavailable. Here, we demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), markedly protected 661W photoreceptor cells from visible light exposure-induced damage at the nanomolar level. We also observed by transmission electron microscopy that light exposure led to severe endoplasmic reticulum (ER) stress in 661W cells as well as abnormal endomembranes and ER membranes. In addition, obvious upregulated ER stress markers were monitored by western blot at the protein level and by quantitative reverse transcription-polymerase chain reaction (RT-PCR) at the mRNA level. Interestingly, rapamycin pretreatment significantly suppressed light-induced ER stress and all three major branches of the unfolded protein response (UPR), including the RNA-dependent protein kinase-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6) pathways both at the protein and mRNA levels. Additionally, the inhibition of ER stress by rapamycin was further confirmed with a dithiothreitol (DTT; a classical ER stress inducer)-damaged 661W cell model. Meanwhile, our results also revealed that rapamycin was able to remarkably inhibit the activation of mTOR and its downstream factors eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), p-4EBP1, p70, p-p70, and phosphorylated ribosomal protein S6 kinase (p-S6K) in the light-injured 661W cells. Thus, these data indicate that visible light induces ER stress in 661W cells; whereas the mTOR inhibitor, rapamycin, effectively protects 661W cells from light injury through suppressing the ER stress pathway.