Enriched Environment Protects the Optic Nerve from Early Diabetes-Induced Damage in Adult Rats

Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Axoglial alterations of the distal (close to the chiasm) optic nerve (ON) could be the first structural change of the visual pathway in streptozotocin (STZ)-induced diabetes in rats. We analyzed the effect of environmental enrichment on axoglial alterations of the ON provoked by experimental diabetes. For this purpose, three days after vehicle or STZ injection, animals were housed in enriched environment (EE) or remained in a standard environment (SE) for 6 weeks. Anterograde transport, retinal morphology, optic nerve axons (toluidine blue staining and phosphorylated neurofilament heavy immunoreactivity), microglia/macrophages (ionized calcium binding adaptor molecule 1 (Iba-1) immunoreactivity), astrocyte reactivity (glial fibrillary acid protein-immunostaining), myelin (myelin basic protein immunoreactivity), ultrastructure, and brain derived neurotrophic factor (BDNF) levels were assessed in non-diabetic and diabetic animals housed in SE or EE. No differences in retinal morphology or retinal ganglion cell number were observed among groups. EE housing which did not affect the STZ-induced weight loss and hyperglycemia, prevented a decrease in the anterograde transport from the retina to the superior colliculus, ON axon number, and phosphorylated neurofilament heavy immunoreactivity. Moreover, EE housing prevented an increase in Iba-1 immunoreactivity, and astrocyte reactivity, as well as ultrastructural myelin alterations in the ON distal portion at early stages of diabetes. In addition, EE housing avoided a decrease in BDNF levels induced by experimental diabetes. These results suggest that EE induced neuroprotection in the diabetic visual pathway.     

Ischemic tolerance protects the rat retina from glaucomatous damage

Glaucoma is a leading cause of acquired blindness which may involve an ischemic-like insult to retinal ganglion cells and optic nerve head. We investigated the effect of a weekly application of brief ischemia pulses (ischemic conditioning) on the rat retinal damage induced by experimental glaucoma. Glaucoma was induced by weekly injections of chondroitin sulfate (CS) in the rat eye anterior chamber. Retinal ischemia was induced by increasing intraocular pressure to 120 mmHg for 5 min; this maneuver started after 6 weekly injections of vehicle or CS and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. Glaucoma was evaluated in terms of: i) intraocular pressure (IOP), ii) retinal function (electroretinogram (ERG)), iii) visual pathway function (visual evoked potentials, (VEPs)) iv) histology of the retina and optic nerve head. Retinal thiobarbituric acid substances levels were assessed as an index of lipid peroxidation. Ischemic conditioning significantly preserved ERG, VEPs, as well as retinal and optic nerve head structure from glaucomatous damage, without changes in IOP. Moreover, ischemia pulses abrogated the increase in lipid peroxidation induced by experimental glaucoma. These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies in glaucoma treatment.     

Clinical and anti-aging effect of mud-bathing therapy for patients with fibromyalgia

This study focuses on two inflammatory diseases, viz., “diabetes mellitus (DM)” that causes serious complications such as retinopathy, nephropathy, and neuropathy, and “ischemic colitis” which is evoked by DM. Ischemic colitis originates from the reduction in mesenteric blood flow to the colon with existence of the occlusive or non-occlusive reasons. Our study objective was to provide early diagnostic approach for ischemic colitis in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley rats were divided into four groups: (i) control use of 0.1 M citrate buffer, the solvent of streptozotocin (C), (ii). induced ischemia (I), (iii) rats subjected to 60 mg/kg STZ intraperitoneally to induce type 1 diabetes (D) (48 h after STZ injection, blood glucose levels >200 mg/dl were considered as diabetic), and (iv) diabetic rats subjected to intestinal ischemia (D+I). The third diabetic group (D) was not operated. At the end of the experimental period, rats were sacrificed, C-reactive protein (CRP) and calprotectin levels were measured in the serum and colon tissue specimens. Tissue specimens were also analyzed histologically. We found that serum and colon calprotectin levels were elevated in the D+I group compared to the D and/or I group alone, but relatively calprotectin levels increased in I as compared to C group in colon tissues. CRP levels were significantly increased with ischemic colitis in diabetes, while colon CRP levels were decreased. These results provide evidence for the existence of inflammation in the STZ-induced diabetic rats with ischemic colitis. In conclusion, our measurements of serum calprotectin levels of STZ-induced diabetic rats with ischemic colitis provide a practical approach for an early diagnosis of ischemic colitis. Furthermore, these biochemical analyses correlate well with the histopathologic findings of STZ-induced diabetic rats with ischemic colitis. Future studies would be desirable to further strengthen the role of calprotectin in the early diagnosis of ischemic colitis in diabetics clinical settings.     

血小板反应素1在STZ诱导大鼠糖尿病性视网膜病变的表达研究

探讨TSP1表达在糖尿病视网膜病变中的作用和机制,为治疗和预防糖尿病视网膜病变提供新的实验和理论依据。用链脲佐菌素(STZ)腹腔注射建立糖尿病模型8周后,采用免疫组织化学、RT-PCR及实时荧光定量PCR法,分析TSP1在早期链尿佐菌素诱导的糖尿病SD大鼠视网膜中的表达。结果显示在早期糖尿病大鼠的视网膜表面血管、神经节细胞层、内外核层中均有明显的TSP1表达,糖尿病视网膜组TSP1 mRNA表达要高于对照组,其中实时荧光定量PCR CT值的结果显示糖尿病组TSP1 mRNA表达量较对照组要高约3．48倍,二组间差别有显著性意义(P<0．01),提示TSP1在视网膜组织中的表达与糖尿病视网膜病变的发生密不可分,TSP1表达的增加可能在糖尿病视网膜病变的发生和发展中起重要作用。     

Environmental Enrichment Protects the Retina from Early Diabetic Damage in Adult Rats

Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Available treatments are not completely effective. We analyzed the effect of environmental enrichment on retinal damage induced by experimental diabetes in adult Wistar rats. Diabetes was induced by an intraperitoneal injection of streptozotocin. Three days after vehicle or streptozotocin injection, animals were housed in enriched environment or remained in a standard environment. Retinal function (electroretinogram, and oscillatory potentials), retinal morphology, blood-retinal barrier integrity, synaptophysin, astrocyte and Müller cell glial fibrillary acidic protein, vascular endothelial growth factor, tumor necrosis factor-α, and brain-derived neurotrophic factor levels, as well as lipid peroxidation were assessed in retina from diabetic animals housed in standard or enriched environment. Environmental enrichment preserved scotopic electroretinogram a-wave, b-wave and oscillatory potential amplitude, avoided albumin-Evan''s blue leakage, prevented the decrease in retinal synaptophysin and astrocyte glial fibrillary acidic protein levels, the increase in Müller cell glial fibrillary acidic protein, vascular endothelial growth factor and tumor necrosis factor-α levels, as well as oxidative stress induced by diabetes. In addition, enriched environment prevented the decrease in retinal brain-derived neurotrophic factor levels induced by experimental diabetes. When environmental enrichment started 7 weeks after diabetes onset, retinal function was significantly preserved. These results indicate that enriched environment could attenuate the early diabetic damage in the retina from adult rats.     

Oxidative stress induces autophagy in response to multiple noxious stimuli in retinal ganglion cells

Retinal ganglion cells (RGCs) are the only afferent neurons that can transmit visual information to the brain. The death of RGCs occurs in the early stages of glaucoma, diabetic retinopathy, and many other retinal diseases. Autophagy is a highly conserved lysosomal pathway, which is crucial for maintaining cellular homeostasis and cell survival under stressful conditions. Research has established that autophagy exists in RGCs after increasing intraocular pressure (IOP), retinal ischemia, optic nerve transection (ONT), axotomy, or optic nerve crush. However, the mechanism responsible for defining how autophagy is induced in RGCs has not been elucidated. Accumulating data has pointed to an essential role of reactive oxygen species (ROS) in the activation of autophagy. RGCs have long axons with comparatively high densities of mitochondria. This makes them more sensitive to energy deficiency and vulnerable to oxidative stress. In this review, we explore the role of oxidative stress in the activation of autophagy in RGCs, and discuss the possible mechanisms that are involved in this process. We aim to provide a more theoretical basis of oxidative stress-induced autophagy, and provide innovative targets for therapeutic intervention in retinopathy.     

Oxidative stress induces autophagy in response to multiple noxious stimuli in retinal ganglion cells

Retinal ganglion cells (RGCs) are the only afferent neurons that can transmit visual information to the brain. The death of RGCs occurs in the early stages of glaucoma, diabetic retinopathy, and many other retinal diseases. Autophagy is a highly conserved lysosomal pathway, which is crucial for maintaining cellular homeostasis and cell survival under stressful conditions. Research has established that autophagy exists in RGCs after increasing intraocular pressure (IOP), retinal ischemia, optic nerve transection (ONT), axotomy, or optic nerve crush. However, the mechanism responsible for defining how autophagy is induced in RGCs has not been elucidated. Accumulating data has pointed to an essential role of reactive oxygen species (ROS) in the activation of autophagy. RGCs have long axons with comparatively high densities of mitochondria. This makes them more sensitive to energy deficiency and vulnerable to oxidative stress. In this review, we explore the role of oxidative stress in the activation of autophagy in RGCs, and discuss the possible mechanisms that are involved in this process. We aim to provide a more theoretical basis of oxidative stress-induced autophagy, and provide innovative targets for therapeutic intervention in retinopathy.     

Insulin Reverses Enhanced Incorporation of 32P into Polyphosphoinositides in Peripheral Nerve of the Streptozotocin Diabetic Rat

The ability of insulin treatment to reverse altered phosphoinositide metabolism in sciatic nerve from streptozotocin diabetic rats was studied. Diabetes was induced in rats by means of a single injection of streptozotocin. Enhanced incorporation of 32P into phosphatidylinositol-4,5-bisphosphate (PIP2) was detectable as early as 8 days following intravenous injection of streptozotocin and was maximal after 4 weeks. Hormone treatment was initiated at this time by daily injections of protamine zinc insulin followed by the implantation of long-acting insulin osmotic minipumps, and 4 weeks later sciatic nerves were removed and incubated in the presence of [32P]orthophosphate. The increased labeling of PIP2 was completely reversed by hormone administration. In contrast, insulin (0.1 and 1.0 mU/ml) added to the incubation medium failed to reverse the altered pattern of 32P incorporation into PIP2. The uptake of 32P into PIP2 was greater than 80% higher into the proximal than into the distal portion of normal sciatic nerve when these were incubated separately. This metabolic difference was abolished in diabetic rats, although the incorporation into both segments was still significantly higher than in controls. These results strengthen the association of altered nerve PIP2 metabolism with the diabetic state and are consistent with the concept that experimental diabetic neuropathy is a distal axonopathy.     

Therapeutic benefit of radial optic neurotomy in a rat model of glaucoma

Radial optic neurotomy (RON) has been proposed as a surgical treatment to alleviate the neurovascular compression and to improve the venous outflow in patients with central retinal vein occlusion. Glaucoma is characterized by specific visual field defects due to the loss of retinal ganglion cells and damage to the optic nerve head (ONH). One of the clinical hallmarks of glaucomatous neuropathy is the excavation of the ONH. The aim of this work was to analyze the effect of RON in an experimental model of glaucoma in rats induced by intracameral injections of chondroitin sulfate (CS). For this purpose, Wistar rats were bilaterally injected with vehicle or CS in the eye anterior chamber, once a week, for 10 weeks. At 3 or 6 weeks of a treatment with vehicle or CS, RON was performed by a single incision in the edge of the neuro-retinal ring at the nasal hemisphere of the optic disk in one eye, while the contralateral eye was submitted to a sham procedure. Electroretinograms (ERGs) were registered under scotopic conditions and visual evoked potentials (VEPs) were registered with skull-implanted electrodes. Retinal and optic nerve morphology was examined by optical microscopy. RON did not affect the ocular hypertension induced by CS. In eyes injected with CS, a significant decrease of retinal (ERG a- and b-wave amplitude) and visual pathway (VEP N2-P2 component amplitude) function was observed, whereas RON reduced these functional alterations in hypertensive eyes. Moreover, a significant loss of cells in the ganglion cell layer, and Thy-1-, NeuN- and Brn3a- positive cells was observed in eyes injected with CS, whereas RON significantly preserved these parameters. In addition, RON preserved the optic nerve structure in eyes with chronic ocular hypertension. These results indicate that RON reduces functional and histological alterations induced by experimental chronic ocular hypertension.     

高压氧在治疗糖尿病视网膜病变中的应用进展

糖尿病视网膜病变是糖尿病最常见、最主要的微血管并发症之一,其高发病率、高致盲率特征严重威胁着人类的健康和生存质量。长期的高糖状态导致视网膜缺血缺氧是糖尿病视网膜病变的主要发病原因。控制高血糖和改善组织缺氧无疑是防治糖尿病微血管病变的有效方法之一。而高压氧治疗是许多急慢性疾病的首选或辅助治疗方法。已有大量证据表明,高压氧治疗对视网膜静脉阻塞及黄斑囊样水肿、缺血性视神经病变、中心性浆液性脉络膜视网膜病变等眼病安全有效。本文就高压氧在糖尿病视网膜病变中的应用进行综述和讨论。     

Optic nerve regeneration after intravitreal peripheral nerve implants: trajectories of axons regrowing through the optic chiasm into the optic tracts

We have studied axon regeneration through the optic chiasm of adult rats 30 days after prechiasmatic intracranial optic nerve crush and serial intravitreal sciatic nerve grafting on day 0 and 14 post-lesion. The experiments comprised three groups of treated rats and three groups of controls. All treated animals received intravitreal grafts either into the left eye after both left sided (unilateral) and bilateral optic nerve transection, or into both eyes after bilateral optic nerve transection. Control eyes were all sham grafted on day 0 and 14 post-lesion, and the optic nerves either unlesioned, or crushed unilaterally or bilaterally. No regeneration through the chiasm was seen in any of the lesioned control optic nerves. In all experimental groups, large numbers of axons regenerated across the optic nerve lesions ipsilateral to the grafted eyes, traversed the short distal segment of the optic nerve and invaded the chiasm without deflection. Regeneration was correlated with the absence of the mesodermal components in the scar. In all cases, axon regrowth through the chiasm appeared to establish a major crossed and a minor uncrossed projection into both optic tracts, with some aberrant growth into the contralateral optic nerve. Axons preferentially regenerated within the degenerating trajectories from their own eye, through fragmented myelin and axonal debris, and reactive astrocytes, oligodendrocytes, microglia and macrophages. In bilaterally lesioned animals, no regeneration was detected in the optic nerve of the unimplanted eye. Although astrocytes became reactive and their processes proliferated, the architecture of their intrafascicular processes was little perturbed after optic nerve transection within either the distal optic nerve segment or the chiasm. The re-establishment of a comparatively normal pattern of passage through the chiasm by regenerating axons in the adult might therefore be organised by this relatively immutable scaffold of astrocyte processes. Binocular interactions between regenerating axons from both nerves (after bilateral optic nerve transection and intravitreal grafting), and between regenerating axons and the intact transchiasmatic projections from the unlesioned eye (after unilateral optic nerve lesions and after ipsilateral grafting) may not be important in establishing the divergent trajectories, since regenerating axons behave similarly in the presence and absence of an intact projection from the other eye.     

Hyperglycemia induces early upregulation of the calcium sensor KChIP3/DREAM/calsenilin in the rat retina

Hyperglycemia alters the tight control of intracellular calcium dynamics in retinal cells and may lead to the development of diabetic retinopathy. The potassium channel interacting protein 3 (KChIP3) also known as DREAM (Downstream Regulatory Element Antagonist Modulator) or calsenilin (KChIP3/DREAM/calsenilin), a member of the neuronal calcium sensor protein family, is expressed in Müller glial cells and upregulated under high glucose experimental culture conditions. Here, we analyzed the expression and function of KChIP3 in the retina of streptozotocin induced diabetic Long Evans rats by immunofluorescence confocal microscopy, western blot, co-immunoprecipitation, whole cell patch clamp recording on isolated cells and KChIP3 gene silencing by RNA interference. Three weeks after streptozotocin application, KChIP3 was increased throughout the different retinal layers and this process was not linked to augmented apoptosis. KChIP3 co-immunoprecipitated with voltage gated K(+) channels of the K(V)4.2-4.3 subtype in retinal extracts from control and hyperglycemic rats. Electrophysiological analysis showed that control cells did not express A type (K(V)4-mediated) K(+) currents but most of the cells from streptozotocin treated retinas displayed macroscopic currents with an inactivating component sensitive to 4-AP, suggesting the persistence of the A type currents at early times after treatment. siRNA analysis in Müller cells cultures grown under high glucose experimental conditions corroborated that, when the expression of KChIP3 is 50% reduced, the number of cells expressing A type currents decreases significantly. Together these data suggest an altered expression and function of KChIP3 after streptozotocin induced hyperglycemia that might help explain some pathological alterations in early diabetic retinopathy.     

Targeting Apoptosis Signalling Kinase-1 (ASK-1) Does Not Prevent the Development of Neuropathy in Streptozotocin-Induced Diabetic Mice

Apoptosis signal-regulating kinase-1 (ASK1) is a mitogen-activated protein 3 kinase (MAPKKK/MAP3K) which lies upstream of the stress-activated MAPKs, JNK and p38. ASK1 may be activated by a variety of extracellular and intracellular stimuli. MAP kinase activation in the sensory nervous system as a result of diabetes has been shown in numerous preclinical and clinical studies. As a common upstream activator of both p38 and JNK, we hypothesised that activation of ASK1 contributes to nerve dysfunction in diabetic neuropathy. We therefore wanted to characterize the expression of ASK1 in sensory neurons, and determine whether the absence of functional ASK1 would protect against the development of neuropathy in a mouse model of experimental diabetes. ASK1 mRNA and protein is constitutively expressed by multiple populations of sensory neurons of the adult mouse lumbar DRG. Diabetes was induced in male C57BL/6 and transgenic ASK1 kinase-inactive (ASK1n) mice using streptozotocin. Levels of ASK1 do not change in the DRG, spinal cord, or sciatic nerve following induction of diabetes. However, levels of ASK2 mRNA increase in the spinal cord at 4 weeks of diabetes, which could represent a future target for this field. Neither motor nerve conduction velocity deficits, nor thermal or mechanical hypoalgesia were prevented or ameliorated in diabetic ASK1n mice. These results suggest that activation of ASK1 is not responsible for the nerve deficits observed in this mouse model of diabetic neuropathy.     

DECREASED AXONAL FLUX OF RETROGRADELY TRANSPORTED GLYCOPROTEINS IN EARLY EXPERIMENTAL DIABETES

Abstract— Anterograde and retrograde flux of axonal transported glycoproteins were examined in streptozotocin diabetic rats with 4 weeks'duration of the metabolic derangement.
[³H]Fucose and [¹⁴C]NeuNAc were injected into the fifth lumbar root ganglion and the accumulation of TCA-PTA insoluble activity proximal and distal to a sciatic nerve ligature was measured.
Accumulation of glycoproteins during 2 h collection periods was decreased distal to a ligature in diabetic animals whereas no abnormality of proximal accumulation was observed. These findings demonstrate an abnormality of the retrograde transport of glycoproteins in early experimental diabetes.     

Statin treatment reduces oxidative stress-associated apoptosis of sciatic nerve in diabetes mellitus

Abstract

Statins are lipid-lowering drugs that are widely used for treating hyperlipidemia, especially in diabetic patients. The aim of our study was to explore the effects of atorvastatin on oxidative stress and apoptosis in the sciatic nerve due to hyperglycemia. Diabetes was induced by streptozotocin. Atorvastatin was given orally for two weeks beginning from the sixth week. Microscopic examination of sciatic nerve revealed that normal tissue organization was disrupted in streptozotocin induced diabetic rats. Treatment with Atorvastatin reduced the histological damage and protected the morphological integrity of the sciatic nerve in streptozotocin induced diabetes. Increased expressions of transforming growth factor beta-1, endothelial nitric oxide synthase and TUNEL in sciatic nerve from streptozotocin induced diabetes were reduced by Atorvastatin. Atorvastatin could improve the effects of oxidative stress and apoptosis on the sciatic nerve due to diabetes.     

Effects of intravitreous sodium hydrosulfide on intraocular pressure and retinopathy in ocular hypertensive rats

We investigated the possible neuroprotectant and intraocular pressure (IOP) lowering effects of intravitreous injection of sodium hydrosulfide (NaSH) in a rodent model of experimental glaucoma. Glaucoma currently is treated by controlling IOP using medications and/or surgery. These methods are not entirely adequate for all patients. We divided 24 rats into three groups. For the control group, the right eye was treated with intravitreous saline. For the glaucoma group, ocular hypertension was induced by photocoagulating three episcleral veins and the limbal plexus of the right eye using an argon laser, then saline was injected into the vitreous of these eyes during the third week. For the NaSH group, rats were treated with intravenous NaSH 3 weeks after photocoagulation. IOP was measured each week during the 6 week experimental period. Coagulating the episcleral veins rapidly increased the IOP of rat eyes. Intravitreous injection of NaSH significantly reduced IOP. Intravitreous NaSH prevented degeneration of the retina and decreased the number of apoptotic cells. Intravitreous NaSH appeared to reduce IOP and to prevent IOP induced retinopathy in rats.     

Diets enriched in PUFAs at an early postimplantation stage prevent embryo resorptions and impaired mTOR signaling in the decidua from diabetic rats

Maternal diabetes increases the risk of embryo resorptions and impairs embryo development. Decidualization is crucial for embryo development and regulated by mTOR signaling. However, little is known about how maternal diabetes affects the decidua at early postimplantation stages and whether dietary treatments enriched in polyunsaturated fatty acids (PUFAs) can prevent decidual alterations. Here, we determined resorption rates, decidual mTOR pathways and markers of decidual function and remodeling in diabetic rats fed or not with diets enriched in PUFAs exclusively during the early postimplantation period. Pregestational streptozotocin-induced diabetic Albino Wistar rats and controls were fed or not with diets enriched in 6% sunflower oil or 6% chia oil (enriched in n-6 or n-3 PUFAs, respectively) on days 7, 8 and 9 of pregnancy and evaluated on day 9 of pregnancy. Maternal diabetes induced an 11-fold increase in embryo resorptions, which was prevented by both PUFAs-enriched diets despite no changes in maternal glycemia. The activity of mTOR pathway was decreased in the decidua from diabetic rats, an alteration prevented by the PUFAs-enriched diets. PUFAs-enriched diets prevented increased expression of Foxo1 (a negative regulator of mTOR) and reduced expression of miR-21 (a negative regulator of Foxo1). These diets also prevented reduced markers of decidual function (leukemia inhibitory factor and IGFBP1 expression and MMPs activity) in diabetic rat decidua. We identified the early post implantation as a crucial stage for pregnancy success, in which dietary PUFAs can protect diabetic pregnancies from embryo resorptions, decidual mTOR signaling impairments, and altered markers of decidual function and remodeling.     

In vivo effect of methylcobalamin on the peripheral nerve structure in streptozotocin diabetic rats

To study in vivo effect of methylcobalamin (CH3-B12) on the peripheral nerve structures, rats with experimental diabetes induced by streptozotocin were administered with daily intramuscular injection of CH3-B12 (500 microgram/kg) for 16 weeks. By isolated nerve fiber studies, CH3-B12-treated diabetic rats showed less incidence of paranodal demyelination as an early sign of segmental demyelination than non-treated diabetic rats. From morphometrical analysis on sural nerves, the reduction in the density of myelinated nerve fibers, nerve fiber size and axon size of myelinated fibers was definitely protected in treated diabetic rats. The results suggested that continuous treatment with CH3-B12 had an ameliorative effect on the peripheral nerve lesions in experimental diabetic neuropathy.     

Early diagnostic value of optical coherence tomography in the clinical prediction model for optic nerve injury in saddle space occupying patients

In this study, 50 patients with anterior ischemic optic neuropathy due to saddle block were selected as the experimental group, and 50 healthy subjects were used as the control group to conduct a study. The best corrected visual acuity examination, optical coherence tomography and visual evoked potential examination were performed on the two groups. The results of the study showed that the majority of patients were middle-aged and older people over the age of 50, but the youngest patients were only 37 years old. After various examinations, it was found that patients with optic nerve injury had a significant reduction in the best corrected visual acuity compared with healthy people. After the onset of the disease, the optic nerve fiber layer will first increase and then decline. During the course of the disease, the patient's optic nerve fiber layer will gradually thin to a much lower level than healthy people. And in comparing the thickness of the optic nerve fiber layer in patients with systemic disease and no systemic disease, it is found that the degree of optic nerve damage is more serious in patients with systemic diseases. After the VEP examination, the difference between the P100 wave latency and the N75-P100 amplitude of the diseased eye and the unaffected eye was statistically significant. Moreover, the difference between the patient's diseased eye and the healthy human eye is almost the same as that of the unaffected eye.