This study aimed to compare the ameliorative effects of Lycii Fructus and Chrysanthemi Flos at different ratios on retinal damage in mice and to elucidate the underlying mechanisms. A retinal injury model was established by intraperitoneal injection of sodium iodate(NaIO_3) solution. The mice were divided into the following groups: blank group, model group, positive drug(AREDS 2) group, low-and high-dose groups of Lycii Fructus and Chrysanthemi Flos at 1∶1, low-and high-dose groups at 3∶1, and low-and high-dose groups at 1∶3. Administration was carried out 15 days after modeling. The visual acuity of the mice was assessed using the black-and-white box test. The fundus was observed using an optical coherence tomography device, and retinal thickness was measured. HE staining was used to observe the morphology and pathological changes of the retina. The levels of oxidative factors in serum and ocular tissues were measured using assay kits. The levels of inflammatory factors in serum and ocular tissues were detected by enzyme-linked immunosorbent assay(ELISA), and the expression of Nrf2, HO-1, and NF-κB proteins in ocular tissues was analyzed by Western blot. The results showed that after administration of Lycii Fructus and Chrysanthemi Flos at different ratios, the model group showed improved retinal thinning and disordered arrangement of retinal layers, elevated content of SOD and GSH in the serum and ocular tissues, and reduced levels of MDA, TNF-α, IL-1β, and IL-6. Lycii Fructus and Chrysanthemi Flos at 1∶1 and 1∶3 showed better improvement effects. The combination significantly upregulated the expression levels of Nrf2 and HO-1 and downregulated the expression of NF-κB p65. These results indicate that Lycii Fructus and Chrysanthemi Flos at different ratios can improve retinal damage, reduce oxidative stress, and alleviate inflammation in both the body and ocular tissues of mice. The mechanism may be related to the regulation of the Nrf2/HO-1 and NF-κB signaling pathways in ocular tissues. These findings provide a theoretical basis for the clinical application of Lycii Fructus and Chrysanthemi Flos in the treatment of dry age-related macular degeneration.
Animals ; Mice ; Retina/injuries* ; Male ; Lycium/chemistry* ; Drugs, Chinese Herbal/administration & dosage* ; Chrysanthemum/chemistry* ; NF-kappa B/genetics* ; Humans ; Retinal Diseases/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress/drug effects* ; Flowers/chemistry* ; Heme Oxygenase-1/genetics*

Neuronal injury in glaucoma persists despite effective intraocular pressure (IOP) control, necessitating neuroprotective strategies for retinal ganglion cells (RGCs). In this study, we investigated the neuroprotective role of the γ-hydroxybutyrate analog HOCPCA in a glaucoma model, focusing on its effects on CaMKII signaling, oxidative stress, and neuroinflammatory responses. Retinal tissue from high IOP animal models was analyzed via proteomics. In vitro mouse retinal explants were subjected to elevated pressure and oxidative stress, followed by HOCPCA treatment. HOCPCA significantly mitigated the RGC loss induced by oxidative stress and elevated pressure, preserving neuronal function. It restored CaMKIIα and β levels, preserving RGC integrity, while also modulating oxidative stress and neuroinflammatory responses. These findings suggest that HOCPCA, through its interaction with CaMKII, holds promise as a neuroprotective therapy for glaucoma.
Animals ; Retinal Ganglion Cells/metabolism* ; Glaucoma/pathology* ; Oxidative Stress/drug effects* ; Neuroprotective Agents/pharmacology* ; Mice ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotection/drug effects* ; Male ; Intraocular Pressure/drug effects*

Objective To investigate the ameliorative effect of salidroside on diabetes retinopathy (DR) rats and its mechanism. Methods Male SD rats were randomly divided into blank group, model group, low-dose and high-dose salidroside treatment groups. Except for the blank group, other groups were modeled by intraperitoneal injection of streptozotocin. After successful modeling, treatment groups were injected intraperitoneally with [50 mg/(kg.d)] and [100 mg/(kg.d)] salidroside respectively, for 4 weeks; the blank group and model group were injected with corresponding doses of saline. ELISA was used to measure the expression levels of antioxidant-related enzyme activity and inflammatory factors in blood glucose and serum of rats in each group. Retinal tissue lesions were detected by HE staining, and the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) in retinal tissues were detected by immunohistochemical staining. Western blot analysis was used to detect the expression of phosphatidylinositol 3 kinase (PI3K) , nuclear factor κB p65 (NF-κB p65), phosphorylated p38 MAPK (p-p38 MAPK), and phosphorylated protein kinase B (p-AKT) proteins. Results Compared with model group, salidroside could significantly reduce blood glucose level and increase body mass in DR rats. The serum levels of superoxide dismutase (SOD) and catalase (CAT) were significantly increased, while the levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and IL-1β were reduced. The protein expression of VEGF, ICAM-1, NF-κB p65 and p-p38 MAPK was significantly decreased, while the protein expression of PI3K and p-AKT was increased. Conclusion Salidroside can reduce DR in rats by inhibiting oxidative stress and immune inflammatory response, which may be related to the reduction of abnormal expression of VEGF and ICAM-1 and the activation of PI3K/AKT signaling pathway.
Animals ; Male ; Rats ; Blood Glucose ; Diabetes Mellitus ; Inflammation/metabolism* ; Intercellular Adhesion Molecule-1/metabolism* ; NF-kappa B/metabolism* ; Oxidative Stress ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Retinal Diseases ; Tumor Necrosis Factor-alpha/metabolism* ; Vascular Endothelial Growth Factor A/metabolism*

BACKGROUNDCollapsin response mediator protein-2 (CRMP2) has been shown to be involved in ischemia/hypoxia (IH) injury. We determined whether CRMP2 modulates ischemic injury in the retinal of Ocular ischemic syndrome (OIS). This study was to explore the molecular mechanisms underlying OIS in a novel mice model.

METHODSExperiments were performed on adult male C57/BL6 mice that received bilateral internal carotid arteries ligation for 1, 2, or 4 weeks. The mice received injection of calpeptin group before occlusion for 4 weeks or not. The expression of CRMP2 in the retinal was examined by western blotting (WB) analysis and immunohistochemical analysis (IHC). The effects of ischemic injury on retinal were evaluated by fundus examination, fundus fluorescein angiography, electroretinogram, cell counting of retinal ganglion cell (RGC), and measurement of the thickness of the retina.

RESULTSThe veins dilated after chronic ischemia. In the electroretinography, the amplitudes of a- and b-waves kept diminishing in an ischemia time-dependent manner. Moreover, the tail vein-retinal circulation time prolonged in the 1- and 2-week group. In comparison, thickness of the retina decreased gradually with the ischemia time elapsed. WB analysis showed the CRMP2 and p-CRMP2 levels decreased in the 2- and 4-week groups. The results of IHC analysis were compatible with our results of WB. The loss of RGCs, decrease of the total reaction time and reduction of CRMP2 was alleviated by intravitreal injection of calpeptin.

CONCLUSIONSThese results revealed that bilateral ligation of the internal carotid artery causes retinal ischemia in mice. Moreover, CRMP2 might play a pivotal role during the ischemic injury in the retina and inhibit the cleavage of CRMP2 can ameliorate the IH injury.

Animals ; Disease Models, Animal ; Electroretinography ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; Ischemia ; genetics ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins ; genetics ; metabolism ; Retinal Diseases ; genetics ; metabolism ; pathology ; Retinal Ganglion Cells ; metabolism ; pathology

The effects of the balance changes of pigment epithelium growth factor (PEDF) and vascular endothelial growth factor (VEGF) in whole-body and retinal tissue on rats with oxygen-induced retinopathy were investigated. Forty-eight neonatal SD rats at the age of 7 days were randomly divided into 4 groups. The neonatal rats in experimental groups were exposed to 75% to 80% oxygen for 5 days and then to normal air, and those in control groups were kept feeding in normal air. At the age of 17 and 22 days, all the neonatal rats received retina angiography with FITC-dextran and the pathological changes of retinal vessels and perfusion were observed. HE staining of the tissue section and the number counting of endothelial cells extending beyond the inner limiting membrane were performed to evaluate the endothelial proliferation. Immunohistochemistry was applied to detect the expression of PEDF and VEGF in retinal tissue, and ELISA to detect their expression in serum. A hypoxic-ischemic proliferation of retina and more endothelial cells extending beyond the inner limiting membrane were found in the neonatal rats in both experimental groups of 17-day old and 22-day old as compared with those in control group with the difference being statistically significant (P<0.01). VEGF staining of the rats in the 17-day old experimental group was significantly stronger, with an increasing positive rate, than that of the rats in the 17-day old control group (P<0.01). PEDF staining of the rats of 22 days old was weaker than that of the rats of 17 days old in the experimental groups (P<0.01). There was no significant difference in serum VEGF concentration among all groups (P>0.05). The serum PEDF concentration in the rats of 17 days old in experimental group was decreased significantly as compared with that in the rats of 17 days old in control group (P<0.01), and in experimental groups, the serum PEDF concentration of the rats of 22 days old was increased as compared with that of the rats of 17 days old (P<0.01). In conclusion, the obviously decreased serum PEDF concentration and the abnormal enhanced expression of VEGF density in local retinal tissue broke down the balance of PEDF/VEGF in whole-body or local tissues, which might play an important role in retinal vascular proliferation.
Animals ; Eye Proteins ; blood ; metabolism ; Nerve Growth Factors ; blood ; metabolism ; Oxygen ; adverse effects ; Rats ; Rats, Sprague-Dawley ; Retina ; metabolism ; Retinal Diseases ; etiology ; metabolism ; Serpins ; blood ; metabolism ; Time and Motion Studies ; Vascular Endothelial Growth Factor A ; blood ; metabolism

The effects of black rice anthocyanidins (BRACs) on retinal damage induced by photochemical stress are not well known. In the present study, Sprague-Dawley rats were fed AIN-93M for 1 week, after which 80 rats were randomly divided into two groups and treated with (n = 40) or without BRACs (n = 40) for 15 days, respectively. After treatment, both groups were exposed to fluorescent light (3,000 +/- 200 lux; 25degrees C), and the protective effect of dietary BRACs were evaluated afterwards. Our results showed that dietary BRACs effectively prevented retinal photochemical damage and inhibited the retinal cells apoptosis induced by fluorescent light (p < 0.05). Moreover, dietary BRACs inhibited expression of AP-1 (c-fos/c-jun subunits), up-regulated NF-kappaB (p65) expression and phosphorylation of IkappaB-alpha, and decreased Caspase-1 expression (p < 0.05). These results suggest that BRACs improve retinal damage produced by photochemical stress in rats via AP-1/NF-kappaB/Caspase-1 apoptotic mechanisms.
Animal Feed/analysis ; Animals ; Anthocyanins/administration & dosage/*pharmacology ; Antioxidants/administration & dosage/*physiology ; Blotting, Western ; Caspase 1/*genetics/metabolism ; Diet ; Dietary Supplements/analysis ; I-kappa B Proteins/genetics/metabolism ; NF-kappa B/*genetics/metabolism ; Neoplasm Proteins/genetics/metabolism ; Nucleocytoplasmic Transport Proteins/genetics/metabolism ; Oryza sativa/chemistry ; Proto-Oncogene Proteins c-fos/genetics/metabolism ; Proto-Oncogene Proteins c-jun/genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Retinal Diseases/etiology/*prevention & control ; Signal Transduction/*drug effects/radiation effects ; Transcription Factor AP-1/*genetics/metabolism

To report the surgical outcome of full-thickness sclerotomy in five cases of uveal effusion syndrome (UES). Full-thickness sclerotomy without sclerectomy was performed on five eyes of four patients with UES with or without nanophthalmos. In four of the eyes, exudative retinal detachment associated with UES resolved after the sclerotomy. The subretinal fluid in one eye, which had a normal axial length, was relieved after undergoing three sclerotomy procedures. Full-thickness sclerotomy without vortex vein decompression or sclerectomy is an effective surgical option for the management of significant UES.
Adult ; Aged ; Drainage/methods ; Exudates and Transudates/*metabolism ; Humans ; Male ; Middle Aged ; Ophthalmologic Surgical Procedures/*methods ; Retinal Detachment/metabolism/surgery ; Sclera/*surgery ; Uveal Diseases/*metabolism/*surgery

OBJECTIVETo investigate the protective effect of Qihuang Mingmu capsule (QHMM) on retina of diabetic mice and its impact on VEGF expression.

METHODForty KK/Upj-Ay mice were randomly divided into the model group and high, middle and low dose QHMM (8.32, 4.16, 2.08 g x kg(-1)) groups. Additional 10 C57BL/6 mice were selected as the control group. Mice were orally administered for three months. Their general appearance, fasting blood-glucose (FBG) and glycosylated hemoglobin (HbA1c) were observed. Pathological changes of retina were observed by light microscope and electron microscope. The expressions of vascular endothelial growth factor (VEGF), growth factor receptors-1 (Flt-1) and growth factor receptors-2 (Flk-1) were examined by Real-time PCR (qPCR) and Western blot.

RESULTQHMM could ameliorate the symptoms of diabetic mice to varying degrees, decrease FBG and HbA1c, alleviate pathological lesions of retina and decrease the expressions of VEGF, Flt-1, Flk-1 mRNA and protein.

CONCLUSIONQHMM has the protective effect on diabetic retinopathy of mice by inhibiting the expressions of VEGF, Flt-1 and Flk-1 and intervening VEGF-VEGFR signal transduction pathway.

Animals ; Capsules ; administration & dosage ; Diabetic Retinopathy ; drug therapy ; genetics ; metabolism ; prevention & control ; Drugs, Chinese Herbal ; administration & dosage ; Gene Expression ; drug effects ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Protective Agents ; administration & dosage ; Retinal Diseases ; drug therapy ; genetics ; metabolism ; prevention & control ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

PURPOSE: We investigated whether oxygen-induced retinopathy (OIR) results in changes in the protein expression of neuronal and inducible nitric oxide synthases (nNOS and iNOS, respectively) in rat model of OIR. In addition, we evaluated whether treatment of rats with triamcinolone acetonide (TA) prevents this response. METHODS: To promote OIR, Sprague-Dawley rats were exposed to hyperoxia from postnatal day 2 (P2) to P14. They were then returned to normoxia after P15. TA was injected into the right vitreous of P15 rats, while saline was injected into the left vitreous. At P18 the expression of nNOS and iNOS was determined using Western blotting and immunostaining techniques in retinas obtained from control rats. RESULTS: In P18 OIR rats, the abundance of nNOS and iNOS protein was significantly increased compared with controls. These increases were not observed in the retinas of rats treated with TA. The change in expression of nNOS and iNOS were specific to parvalbumin and glial fibrillary acidic protein-positive cells. Treatment with TA prevented the increased expression of nNOS and iNOS in all samples. CONCLUSIONS: Hypoxia upregulates expression of nNOS and iNOS in OIR rat retinas, which is can be prevented by treatment with TA.
Animals ; Animals, Newborn ; Anoxia/metabolism/pathology/*prevention & control ; Blotting, Western ; Disease Models, Animal ; Female ; Glucocorticoids/pharmacology ; Immunohistochemistry ; Neurons/metabolism ; Nitric Oxide Synthase Type II/*biosynthesis ; Oxygen/toxicity ; Pregnancy ; *Pregnancy, Animal ; Rats ; Rats, Sprague-Dawley ; Retina/*metabolism/pathology ; Retinal Diseases/chemically induced/pathology/*prevention & control ; Triamcinolone Acetonide/*pharmacology

PURPOSE: To evaluate the expression of the Na(+)-K(+)-2Cl(-)-cotransporter 2 (NKCC2) in the ischemic rat retina. METHODS: Retinal ischemia was induced by pressures 90 to 120 mmHg, above systemic systolic pressure. Immunohistochemistry and western blot analysis were performed. RESULTS: NKCC2 is expressed in the normal retina and its expression is increased by ischemia caused by intraocular pressure elevation. NKCC2 immunoreactivity was observed mainly in axon bundles of ganglion cells and horizontal cell processes in the retina. NKCC2 expression continuously increased with a peak value 3 days (to 415% of normal levels) after ischemic injury, and then gradually decreased to 314% of controls until 2 weeks post injury. The mean density of NKCC2-labeled ganglion cells per mm2 changed from 1,255 +/- 109 in normal retinas to 391 +/- 49 and 185 +/- 37 at 3 days and 2 weeks after ischemia, respectively (p < 0.05), implying cell death of ganglion cells labeled with NKCC2. CONCLUSIONS: Taken together, these results suggest that NKCC2, which is expressed in retinal ganglion and horizontal cells, may contribute to cell death by ischemic injury in the retina, although the molecular mechanisms involved remain to be clarified.
Animals ; Blotting, Western ; Disease Models, Animal ; Immunohistochemistry ; Intraocular Pressure ; Ischemia/etiology/*metabolism ; Male ; Microscopy, Confocal ; Ocular Hypertension/*complications/metabolism/physiopathology ; Rats ; Rats, Sprague-Dawley ; Retinal Diseases/etiology/*metabolism ; Retinal Ganglion Cells/*metabolism/pathology ; Sodium-Potassium-Chloride Symporters/*biosynthesis