Controlled Elevation of Intraocular Pressure (CEI) Glaucoma Model in Rats.

Experimental elevation of intraocular pressure (IOP), a major glaucoma risk factor, has been a mainstay of research into mechanisms of glaucomatous optic nerve damage for decades. Methods that produce sustained IOP elevation can mimic the chronic nature of glaucoma and produce optic nerve damage. However, the pressure course for individual animals can be variable, unpredictably high at times, and difficult to monitor with current tonometry methods. All of this can complicate correlations of pressure history with axonal injury. An alternative is to control the extent and duration of IOP elevation over a period of several hour-long enough to produce axonal injury and gene expression changes within the optic nerve head that may indicate cellular mechanisms of glaucomatous optic nerve damage. The prolonged general anesthesia that this requires does have the potential to reduce systemic blood pressure, which may contribute to axonal injury in the face of elevated IOP. This chapter will describe our Controlled Elevation of IOP (CEI) model in laboratory rats. We will include methods for applying this to several animals at a time, as well as how to maintain blood pressure, oxygenation, and body temperature to ensure that the resulting injury and tissue events reflect the effects of elevated IOP on optic nerve tissues and not simply reduced ocular perfusion and ischemia.

In Vitro and In Vivo Methods for Studying Retinal Ganglion Cell Survival and Optic Nerve Regeneration.

Glaucoma is marked by a progressive degeneration of the optic nerve and delayed loss of retinal ganglion cells (RGCs), the projection neurons of the eye. Because RGCs are not replaced and because surviving RGCs cannot regenerate their axons, the visual loss in glaucoma is largely irreversible. Here we describe methods to evaluate treatments that may be beneficial for treating glaucoma using in vitro cell culture models (immunopanning to isolate neonatal RGCs, dissociated mature retinal neurons, retinal explants) and in vivo models that test potential treatments or investigate underlying molecular mechanisms in an intact system. Potentially, the use of these models can help investigators continue to improve treatments to preserve RGCs and restore visual function in patients with glaucoma.

Translational Research and Therapies for Neuroprotection and Regeneration of the Optic Nerve and Retina: A Narrative Review.

Most retinal and optic nerve diseases pose significant threats to vision, primarily due to irreversible retinal neuronal cell death, a permanent change, which is a critical factor in their pathogenesis. Conditions such as glaucoma, retinitis pigmentosa, diabetic retinopathy, and age-related macular degeneration are the top four leading causes of blindness among the elderly in Japan. While standard treatments-including reduction in intraocular pressure, anti-vascular endothelial growth factor therapies, and retinal photocoagulation-can partially delay disease progression, their therapeutic effects remain limited. To address these shortcomings, a range of neuroprotective and regenerative therapies, aimed at preventing retinal neuronal cell loss, have been extensively studied and increasingly integrated into clinical practice over the last two decades. Several of these neuroprotective therapies have achieved on-label usage worldwide. This narrative review introduces several neuroprotective and regenerative therapies for retinal and optic nerve diseases that have been successfully translated into clinical practice, providing foundational knowledge and success stories that serve as valuable references for researchers in the field.

Leukemic occult infiltrative optic neuropathy presenting as optic neuritis: a case report.

Isolated ocular relapses of leukemia are rare and typically present as infiltrative lesions of the optic nerve. This report presents a case of an isolated ocular relapse of leukemia in a female patient, characterized by occult infiltrative optic neuropathy. Despite the absence of leukemic cell infiltration on MRI, a 33-year-old female patient presented with optic neuritis, which resolved after intrathecal administration of chemotherapeutic agents. However, due to her non-compliance with the treatment regimen, leukemia progressed to infiltrative optic neuropathy. She refused radiation therapy, and while intrathecal injections provided temporary stabilization, they were insufficient for sustained disease control. This case uniquely documents the extended progression of an isolated ocular relapse of leukemia, evolving from an occult infiltrative lesion initially presenting as optic neuritis to a more pronounced infiltrative lesion. It suggests that leukemic optic nerve infiltration can occur in patients with leukemia even in the absence of MRI-detectable abnormalities. Radiation therapy emerges as a critical modality in the management of infiltrative lesions of the optic nerve.

Perioperative and postoperative effects of hydrostatic pressure applied to the dura mater on central nervous system in unilateral biportal endoscopic spine surgery.

OBJECTIVES: To evaluate the changes in optic nerve sheath diameter (ONSD) caused by this pressure applied to the dura mater and postoperative complications. METHODS: The study was conducted between 01.01.2022 and 01.06.2022 at Private Medicabil Hospital. The ONSD was measured 3 mm behind the eyeball using US at 5 time points: T1 (in the supine position after anesthesia induction), T2 (after conversion to the prone position), T3 (in the prone position after applying pressure to the dura mater), T4 (in the prone position after the discontinuation of applying pressure to the dura mater), T5 (after conversion to the supine position). Postoperative complications were recorded. RESULTS: The ONSD at T3 was higher than those at all time points. For an ONSD value >5.3 mm, the sensitivity, specificity, positive predictive, and negative predictive values were 87.5%, 71.9%, 50.9%, and 94.5%, respectively (Area under the curve 0.830, 95% Confidence Interval: 0.761-0.899, p<0.001) CONCLUSION: We think that the hydrostatic pressure applied to the dura mater in unilateral biportal endoscopic (UBE) surgeries causes changes in the ONSD sheath diameter and that monitoring ONSD with peroperative USG can reduce the possible complications in order to reduce the effects of this pressure on the central nervous system.

An efficacy of protection the organs at risks comparison between the intensitymodulated radiotherapy therapy (IMRT) and the three-dimensional conformal radiotherapy (3DCRT).

OBJECTIVE: To compare the efficiency of three-dimensional conformal radiotherapy and intensity-modulated radiation therapy techniques. Method: The cross-sectional study was conducted from February to August 2021 at Al-Amal National Hospital, Baghdad, Iraq, and comprised patients aged 19-45 years with cancerous head and neck tumours of size 2-7cm. All the patients underwent magnetic resonance imaging or computed tomography simulation scans. Treatment planning techniques used for each patient were three-dimensional conformal radiotherapy and intensitymodulated radiotherapy. After evaluating patterns, a better plan and treatment with an X-ray beam was chosen. Data was analysed using SPSS 24. Results: The study involved thirty participants, with 17(57%) females and 13(43%) males, aged 19-45, and 28 patients having chemotherapy. Six out of thirty had craniotomy surgery. The intensity-modulated radiation therapy had a safer radiation dose than the three-dimensional conformal radiotherapy for spinal cord (p=0.3203), brain stem (p= 0.17924), right parotid gland (p=0.8556) and left parotid gland (p=0.2193). The three-dimensional conformal radiotherapy protected the organs better than intensity-modulated radiation therapy for left optic nerve (p=0.1227), right optic nerve (p=0.0032), left eye (p=0.3859), right eye (p=0.1189), left lens (p=0.0004), right lens (p=0.0001), optic chiasm (p=0.0320) and pituitary gland (p=0.9162). CONCLUSIONS: The intensity-modulated radiation therapy technique protected the spinal cord, brain stem, and right and left parotid glands. The three-dimensional conformal radiotherapy was safe for left and right optic nerves, left and right eyes, left and right lenses, optic chiasm and pituitary glands.

[Research progress of retinal neuroprotective drugs for glaucoma].

Glaucoma is a neural degenerative disease characterized by progressive loss of retinal ganglion cells, resulting in irreversible visual field loss, low vision, and total blindness. Despite the fact that the pathological elevation of intraocular pressure is a major risk factor for glaucoma, it is imperative to develop therapies that can prevent and block retinal ganglion cell injury and apoptosis in addition to reducing intraocular pressure. Drug therapy is the primary treatment for glaucoma in most clinical cases. This article provides reference information for the clinical treatment of glaucoma by summarizing and analyzing the medications that have direct optic nerve protection in clinical or preclinical trials, based on the most recent research results from both domestic and international studies.

The utility of MRI radiological biomarkers in determining intracranial pressure.

Intracranial pressure (ICP) is a physiological parameter that conventionally requires invasive monitoring for accurate measurement. Utilising multivariate predictive models, we sought to evaluate the utility of non-invasive, widely accessible MRI biomarkers in predicting ICP and their reversibility following cerebrospinal fluid (CSF) diversion. The retrospective study included 325 adult patients with suspected CSF dynamic disorders who underwent brain MRI scans within three months of elective 24-h ICP monitoring. Five MRI biomarkers were assessed: Yuh sella grade, optic nerve vertical tortuosity (VT), optic nerve sheath distension, posterior globe flattening and optic disc protrusion (ODP). The association between individual biomarkers and 24-h ICP was examined and reversibility of each following CSF diversion was assessed. Multivariate models incorporating these radiological biomarkers were utilised to predict 24-h median intracranial pressure. All five biomarkers were significantly associated with median 24-h ICP (p < 0.0001). Using a pair-wise approach, the presence of each abnormal biomarker was significantly associated with higher median 24-h ICP (p < 0.0001). On multivariate analysis, ICP was significantly and positively associated with Yuh sella grade (p < 0.0001), VT (p < 0.0001) and ODP (p = 0.003), after accounting for age and suspected diagnosis. The Bayesian multiple linear regression model predicted 24-h median ICP with a mean absolute error of 2.71 mmHg. Following CSF diversion, we found pituitary sella grade to show significant pairwise reversibility (p < 0.001). ICP was predicted with clinically useful precision utilising a compact Bayesian model, offering an easily interpretable tool using non-invasive MRI data. Brain MRI biomarkers are anticipated to play a more significant role in the screening, triaging, and referral of patients with suspected CSF dynamic disorders.

Evaluation of optic nerve sheath diameter in patients undergoing laparoscopic surgery in the Trendelenburg position: a prospective observational study.

BACKGROUND: The Trendelenburg position and pneumoperitoneum may cause cerebral edema and increased intracranial pressure. Non-invasive measurement of the diameter of the optic nerve sheath by ultrasonography can provide early recognition of intracranial pressure. OBJECTIVE: Evaluate the optic nerve sheath diameter (ONSD) changes in patients who undergo laparoscopic surgery in the Trendelenburg position and make indirect conclusions about changes in intracranial pressure. DESIGN: Prospective, observational. SETTING: Laparoscopic surgeries. PATIENTS AND METHODS: Patients aged 18-75 years who underwent laparoscopic surgery in the Trendelenburg position under general anesthesia were included in our study. The ONSD was measured four times: Immediately after tracheal intubation, in the neutral position (baseline value) (T0), 10 minutes after pneumoperitoneum and Trendelenburg position (T1), 60 minutes after pneumoperitoneum and Trendelenburg position (T2), and 10 minutes after the pneumoperitoneum is terminated and placed in the neutral position (T3). MAIN OUTCOME MEASURES: Compare ONSD measured by ultrasonography at different times of surgery. SAMPLE SIZE: 40. RESULTS: Arterial carbon dioxide pressure increased with laparoscopy and Trendelenburg position in parallel with ONSD measurements and decreased again after returning to the neutral position. It was still higher than the baseline value at the T3. There was also a significant difference[a] between the measurement made at the T2 and the measurement made at T1. This difference showed that the prolongation of the Trendelenburg time was associated with an increase in ONSD. At the end of the operation it was observed that the decreased statistically significantly (T3) 10 minutes after the pneumoperitoneum was terminated and the position was corrected. However, the ONSD was still higher at the end of the operation (T3) compared to the baseline value measured at the beginning of the operation (T0). CONCLUSION: The ONSD increased in relation to Trendelenburg position and pneumoperitoneum. With these results, we think the ultrasonographic measurement of ONSD, a non-invasive method, can be used for clinical follow-up when performing laparoscopic surgery in the Trendelenburg position in cases requiring intracranial pressure monitoring. LIMITATIONS: There may be variations in the measurement of ONSD, even in the measurements of the same practitioner, as in all imaging with an ultrasonography device.

The optic nerve sheath in hypertensive disorders of pregnancy and perinatal outcomes: a cohort study.

BACKGROUND: Preeclampsia is implicated in 14% of maternal deaths worldwide, mostly due to complications such as intracranial hemorrhage and cerebral edema. Cerebral edema increases intracranial pressure, which can be predicted by ultrasonographic measurement of the optic nerve sheath diameter (ONSD). Greater diameters have been reported in women with preeclampsia and eclampsia; however, data are lacking on the possible association with maternal and neonatal adverse outcomes. This study aimed to determine whether there is an association between hypertensive disorders of pregnancy and the ONSD, and between this measurement and maternal and neonatal adverse outcomes. METHODS: This was a cohort study involving 183 women in the third trimester of pregnancy or within 24 h following childbirth, distributed as follows: control group (n = 30), gestational hypertension (n = 14), chronic hypertension (n = 12), preeclampsia without severe features (n = 12), preeclampsia with severe features (n = 62), superimposed preeclampsia (n = 23) and eclampsia (n = 30). The participants underwent ocular ultrasonography, and data on maternal and neonatal outcomes were collected from the medical records. To compare the groups, analysis of variance was used for the normally distributed numerical variables and the Kruskal-Wallis test was used for variables with non-normal distribution. Two-tailed p-values ≤ 0.05 were considered statistically significant. RESULTS: Overall comparison between the seven groups showed no statistically significant difference in the mean ONSD (p = 0.056). Nevertheless, diameters were significantly greater in the eclampsia group compared to the control group (p = 0.003). Greater diameters were associated with maternal admission to the intensive care unit (ICU) (p < 0.01) and maternal near miss (p = 0.01). There was no association between ONSD and admission to the neonatal ICU (p = 0.1), neonatal near miss (p = 0.34) or neonatal death (p = 0.26). CONCLUSIONS: No association was found between ONSD and the hypertensive disorders of pregnancy in the overall analysis; however, ONSD was greater in women with eclampsia compared to controls. Greater diameters were associated with maternal admission to the ICU and maternal near miss. These findings suggest a potential use for bedside ultrasound as an additional tool for stratifying risk in patients with hypertensive disorders of pregnancy.

The brain-eye connection: More than just action potentials.

In this issue of the Journal of Experimental Medicine, Cao et al. (https://doi.org/10.1084/jem.20240386) demonstrate that the connection between the eye and the brain goes beyond the impulses carried by the optic nerve and that in Alzheimer's disease (AD), the influx of toxic Aß from the brain to the retina underlies AD-induced retinal degeneration.

Demyelination and neurodegeneration early in experimental autoimmune encephalomyelitis contribute to functional deficits in the anterior visual pathway.

Impaired visual function is a prevalent feature of optic neuritis (ON) in multiple sclerosis (MS). Abnormal visual evoked potential (VEP) findings of increased latencies, reduced amplitudes and abnormal waveforms as well as decreased retinal nerve fiber layer (RNFL) assessed by optical coherence tomography (OCT) are hallmarks of ON-induced visual dysfunction. Here we utilized the experimental autoimmune encephalomyelitis (EAE) mouse model of MS to investigate the functional and pathological progression during early (before any clinical symptoms), peak (initial maximal clinical symptoms), and late (chronic disease for > 3 weeks) disease stages. Demyelination and initial stages of axon damage were observed in early EAE. Significant demyelination, inflammation, increased axon damage and impaired P1/N2 amplitudes and latencies by VEP were seen in middle and late EAE groups. A decrease in RNFL thickness by OCT was observed only during late EAE. NanoString analysis of optic nerves from late EAE indicated elevated inflammation-related genes, reduced myelin-related genes, and changes in axon degeneration-related genes. Early inflammatory demyelination and functional deficits of the visual pathway, if untreated, may lead to severe irrecoverable axon damage in EAE. These studies potentially help explain the progression of visual dysfunction during MS.

Effect of needle types and diameters using in spinal anesthesia on optic nerve sheath diameter: Prospective randomized study.

BACKGROUND: This prospective randomized study aimed to investigate the impact of needle types and diameters used in spinal anesthesia (SA) on optic nerve sheath diameter (ONSD) in patients undergoing lower extremity orthopedic surgery. METHODS: Patients were randomly assigned to 3 groups based on the needle type and size used for SA: Group 25w (25 gauge Whitacre needle), Group 27q (27 gauge Quincke needle), and Group 25q (25 gauge Quincke needle). Initially, 165 patients (55 in each group) were enrolled, with 146 patients ultimately included in the analysis (Group 25w, n = 49; Group 27q, n = 48; Group 25q, n = 49). ONSD measurements were conducted using ultrasound guidance at 5 time points: T0 (pre-SA), T1 (5 minutes post-SA), T2 (5 minutes post-tourniquet inflation), T3 (5 minutes post-tourniquet deflation), and T4 (24 hours post-operation). Additionally, oxygen saturation, systolic arterial pressure, mean arterial pressure, diastolic arterial pressure, and heart rate were recorded at these time points. RESULTS: Analysis of ONSD measurements revealed no significant differences among the groups at time points T0,T1,T2, and T4 (P = .7293, P = .4428, P = .3676, and P = .3667, respectively). However, at T3, ONSD values were significantly higher in Group 27q compared to Group 25q (P = .0325). Across all groups, the mean ONSD values measured post-tourniquet release (T3) were higher than those at T0,T2, and T4 (P < .001 for all). The incidence of nausea was similar among the groups, and no cases of headache or visual impairment were reported within the initial 24 hours post-surgery. CONCLUSION: In conclusion, our study suggests that while subarachnoid injection and tourniquet inflation do not impact intracranial pressure (ICP), tourniquet deflation leads to an increase in ICP during lower limb surgery under SA. Therefore, caution should be exercised when using a tourniquet in patients at risk of elevated ICP.

Rapid Amplification of Cerebrospinal Fluid Pressure as a Possible Mechanism for Optic Nerve Sheath Bleeding in Infants With Nonaccidental Head Injury.

Purpose: Subdural hemorrhage along the optic nerve (ON) is a histopathological indicator of abusive head trauma (AHT) in infants. We sought to determine if this bleeding could be caused by an abrupt increase in intracranial pressure transmitted to cerebrospinal fluid (CSF) at the optic foramen (OF). Methods: A theoretical model is developed to simulate the effect of a pressure perturbation of maximal amplitude P applied at the optic foramen for a short duration T on the CSF-filled ON subarachnoid space (ONSAS). The ONSAS is modelled as a fluid-filled channel with an elastic wall representing the flexible ONSAS-arachnoid/dura interface. A constitutive law describing the relationship between CSF pressure and ONSAS deformation is inferred from published measurements. CSF pressure profiles along the ONSAS are examined systematically over a broad range of P and T. Results: The pressure perturbation initiated at the OF produces a pressure wave that stretches the ONSAS. This wave propagates rapidly along the ONSAS toward the scleral end of the ON, where it is reflected back toward the brain. For sufficiently small T a shock wave with amplification up to six times larger than P over a timescale of tens of milliseconds is observed at the scleral end of the ON. Comparatively smaller amplifications are observed for slower perturbations. Conclusions: A sudden increase in CSF pressure in the cranial cavity can cause a rapid expansion of the ONSAS, which may lead to rupture of the bridging blood vessels. Our study predicts a plausible mechanism for subdural hemorrhage that occurs in abusive head trauma in infants.

Delayed Surgical Reversal of Optic Nerve Compression Leads to Exponential Degeneration of Optic Nerve Fibers and Selective Sparing of the Small Fibers.

Purpose: To evaluate the effectiveness of surgical reversal of experimental optic nerve compression in treating persistent compressive optic neuropathy and to explore the relationship between surgical outcomes and the timing of the procedure. Methods: Surgical reversal procedures (decompression surgery) were conducted at five time intervals: 1, 3, and 7 days and 2 and 3 weeks following optic nerve compression in a rabbit model. The groups were labeled as DC-1d, DC-3d, DC-7d, DC-2w, and DC-3w, respectively. The study investigated changes in ganglion cell complex (GCC) thickness using spectral-domain optical coherence tomography and the percentage of surviving retinal ganglion cells (RGCs) through immunofluorescence staining and optic nerve axons stained with p-phenylenediamine at 4 weeks after decompression. Additionally, the area distribution of surviving axons was analyzed. Results: The decline in GCC thickness was halted following decompression. The remaining thickness of the GCC in group DC-1d was found to be statistically significantly higher at 2, 3, and 4 weeks postonset compared to the no-decompression group. Similarly, GCC thickness in group DC-3d was significantly higher at 3 and 4 weeks postonset. The percentage of surviving RGCs and axons at 4 weeks postonset exhibited an exponential correlation with the onset time of decompression, with R2 values of 0.72 and 0.78, respectively. The surviving axon area declined following delayed decompression. Conclusions: Persistent substantial compression on the optic nerve leads to exponential degeneration of the optic nerve, initially affecting larger optic nerve fibers. Early intervention aimed at relieving the compression on the optic nerve may offer potential benefits in mitigating the degenerative effects and conserving visual function.

Rotenone-Induced Optic Nerve Damage and Retinal Ganglion Cell Loss in Rats.

Rotenone is a mitochondrial complex I inhibitor that causes retinal degeneration. A study of a rat model of rotenone-induced retinal degeneration suggested that this model is caused by indirect postsynaptic N-methyl-D-aspartate (NMDA) stimulation triggered by oxidative stress-mediated presynaptic intracellular calcium signaling. To elucidate the mechanisms by which rotenone causes axonal degeneration, we investigated morphological changes in optic nerves and the change in retinal ganglion cell (RGC) number in rats. Optic nerves and retinas were collected 3 and 7 days after the intravitreal injection of rotenone. The cross-sections of the optic nerves were subjected to a morphological analysis with axon quantification. The axons and somas of RGCs were analyzed immunohistochemically in retinal flatmounts. In the optic nerve, rotenone induced axonal swelling and degeneration with the incidence of reactive gliosis. Rotenone also significantly reduced axon numbers in the optic nerve. Furthermore, rotenone caused axonal thinning, fragmentation, and beading in RGCs on flatmounts and decreased the number of RGC soma. In conclusion, the intravitreal injection of rotenone in rats induced morphological abnormities with a reduced number of optic nerve axons and RGC axons when the RGC somas were degenerated. These findings help elucidate the pathogenesis of optic neuropathy induced by mitochondrial dysfunction.

The Neuroprotective Effect of Erythropoietin on the Optic Nerve and Spinal Cord in Rats with Experimental Autoimmune Encephalomyelitis through the Activation of the Extracellular Signal-Regulated Kinase 1/2 Signaling Pathway.

Experimental autoimmune encephalomyelitis is a demyelinating disease that causes paralysis in laboratory rats. This condition lacks treatment that reverses damage to the myelin sheaths of neuronal cells. Therefore, in this study, treatment with EPO as a neuroprotective effect was established to evaluate the ERK 1/2 signaling pathway and its participation in the EAE model. EPO was administered in 5000 U/Kg Sprague Dawley rats. U0126 was used as an inhibitor of the ERK 1/2 pathway to demonstrate the possible activation of this pathway in the model. Spinal cord and optic nerve tissues were evaluated using staining techniques such as H&E and the Luxol Fast Blue myelin-specific technique, as well as immunohistochemistry of the ERK 1/2 protein. The EPO-treated groups showed a decrease in cellular sampling in the spinal cord tissues but mainly in the optic nerve, as well as an increase in the expression of the ERK 1/2 protein in both tissues. The findings of this study suggest that EPO treatment reduces cellular death in EAE-induced rats by regulating the ERK pathway.

[Concentration of gilteritinib in the cerebrospinal fluid of a patient with relapsed FLT3-ITD positive acute myeloid leukemia with optic nerve involvement].

A 72-year-old woman with relapsed FLT3-ITD-positive acute myeloid leukemia was treated with gilteritinib and achieved complete remission with incomplete hematological recovery. However, two months later, she developed optic nerve infiltration and lost vision in her right eye while maintaining hematological remission on gilteritinib. Intrathecal injection of cytotoxic drugs reduced the number of blasts in the cerebrospinal fluid (CSF), but her vision did not recover. At the onset of optic nerve infiltration, at a dose of 80 mg/day gilteritinib, the plasma trough and CSF levels of gilteritinib were 151.9 ng/ml and 1.9 ng/ml, respectively, with a central nervous system (CNS) penetration rate of 1.3%. Hematologic progressive disease (PD) was detected after 40 days, and the patient died one month later. Target sequencing at the time of hematologic PD revealed the FLT3 F691L mutation, which is known to confer resistance to gilteritinib. In this patient, pharmacokinetic (low CNS penetration of gilteritinib) and pharmacodynamic (acquisition of a drug resistance mutation) mechanisms were thought to be responsible for the CNS relapse and hematologic PD, respectively. We believe this is a valuable case to report considering the scarcity of data on CNS penetration of FLT3 inhibitors and their effects on CNS disease in the literature.

Inhibition of CRMP2 Phosphorylation Suppresses Microglia Activation in the Retina and Optic Nerve and Promotes Optic Nerve Regeneration After Optic Nerve Injury.

As the primary connection between the eye and brain, the optic nerve plays a pivotal role in visual information transmission. Injuries to the optic nerve can occur for various reasons, including trauma, glaucoma, and neurodegenerative diseases. Retinal ganglion cells (RGCs), a type of neurons that extend axons through the optic nerve, can rapidly respond to injury and initiate cell death. Additionally, following optic nerve injury microglia, which serve as markers of neuroinflammation, transition from a resting state to an activated state. The phosphorylation of collapsin response mediator protein2 (CRMP2) in the semaphorin 3A (Sema3A) signalling pathway affects several processes, including axon guidance and neuron regeneration. In this study, we used an optic nerve crush (ONC) mouse model to investigate the effects of suppressing CRMP2 phosphorylation on microglia activation. We found that CRMP2 phosphorylation inhibitor suppressed RGCs loss and promoted neuronal regeneration following ONC. In addition, CRMP2 S522A mutant (CRMP2 KI) mice exhibited decreased microglial activation in both the retina and optic nerve following ONC. These results suggest that inhibiting the phosphorylation of CRMP2 can alleviate the loss of RGCs and microglial activation after optic nerve injury, providing insight into the development of treatments for optical neuropathies and neurodegenerative diseases.