Traumatic Optic Nerve Research Articles

Caspase-3 inhibitor Z-DEVD-FMK enhances retinal ganglion cell survival and vision restoration after rabbit traumatic optic nerve injury.

Vision loss after traumatic optic nerve injury is considered irreversible because of the retrograde loss of retinal ganglion cells (RGCs) which undergo apoptosis. Because the second messenger caspase-3 plays a major role in apoptosis, we now evaluated the efficacy of the specific caspase-3 inhibitor, Z-DEVD-FMK, in a rabbit model of fluid percussion injury (FPI) which mimics traumatic optic nerve injury in humans to enhance cell survival and improve vision. Survival of RGCs and recovery of vision were studied using retinal morphological markers and visual evoked potentials (VEP), respectively. The FPI traumatized animals were treated in their right eye with a single intravitreal or peribulbar injection of Z-DEVD-FMK 30 min post-injury compared to 2% DMSO control injections in their left eye. Intravitreal Z-DEVD-FMK, but not control injections, led to down-regulation of capase-3 and reduced, in a dose-dependent manner, RGCs apoptosis from 7 to 21 days post-injury. These morphological improvements were accompanied by vision restoration as documented by VEP. The neuroprotection after intravitreal injection of Z-DEVD-FMK was more effective than the peribulbar application. The caspase-3 inhibitor Z-DEVD-FMK is neuroprotective by inhibiting RGCs apoptosis when injected 30 min after optic nerve damage and significantly promotes restoration of vision. A controlled clinical trial is now needed to evaluate the efficacy and safety of Z-DEVD-FMK in humans.

Brilliant blue G treatment facilitates regeneration after optic nerve injury in the adult rat.

Injuries to the adult mammalian visual system often lead to functional deficits with little or no chance of spontaneous recovery. Previous studies in rats have demonstrated beneficial effects of inhibition of the P2X7 receptor with brilliant blue G (BBG) after spinal cord injury; however, little is known about BBG as a potential treatment strategy for optic nerve injuries. Adult Sprague-Dawley rats were subjected to a controlled optic nerve crush lesion and randomized to treatment with BBG (50 mg/kg body weight intravenously) or vehicle for 2 days after injury. The temporal pattern of axonal breakdown and regeneration, as well as formation of the glial scar and microglia/macrophage activation, was studied at 7, 14, and 28 days after lesion induction by immunohistochemical analysis. Results show reduced glial scar formation, less macrophage activation, and signs indicative of axonal regeneration beyond the glial scar in treated animals. No significant side effects from the treatment were observed. Effects on axonal breakdown, regeneration, and glial scar formation are discussed in relation to the proposed beneficial effects of BBG treatment. The present study demonstrates positive effects of BBG treatment on neural repair after traumatic optic nerve injury, and also shows its feasibility as a proposed future clinical treatment strategy.

Tumor necrosis factor alpha has an early protective effect on retinal ganglion cells after optic nerve crush.

BackgroundGlaucoma is an optic neuropathy that is characterized by the loss of retinal ganglion cells (RGCs) initiated by damage to axons in the optic nerve. The degeneration and death of RGCs has been thought to occur in two waves. The first is axogenic, caused by direct insult to the axon. The second is somatic, and is thought to be caused by the production of inflammatory cytokines from the activated retinal innate immune cells. One of the cytokines consistently linked to glaucoma and RGC damage has been TNFα. Despite strong evidence implicating this protein in neurodegeneration, a direct injection of TNFα does not mimic the rapid loss of RGCs observed after acute optic nerve trauma or exposure to excitotoxins. This suggests that our understanding of TNFα signaling is incomplete.MethodsRGC death was induced by optic nerve crush in mice. The role of TNFα in this process was examined by quantitative PCR of Tnfα gene expression, and quantification of cell loss in Tnfα−/− mice or in wild-type animals receiving an intraocular injection of exongenous TNFα either before or after crush. Signaling pathways downstream of TNFα were examined by immunolabeling for JUN protein accumulation or activation of EGFP expression in NFκB reporter mice.ResultsOptic nerve crush caused a modest increase in Tnfα gene expression, with kinetics similar to the activation of both macroglia and microglia. A pre-injection of TNFα attenuated ganglion cell loss after crush, while ganglion cell loss was more severe in Tnfα−/− mice. Conversely, over the long term, a single exposure to TNFα induced extrinsic apoptosis in RGCs. Müller cells responded to exogenous TNFα by accumulating JUN and activating NFκB.ConclusionEarly after optic nerve crush, TNFα appears to have a protective role for RGCs, which may be mediated through Müller cells.

Diagnosis and treatment of optic nerve trauma.

Decreasing visual acuity secondary to orbital trauma or orbital and anterior skull base surgery may be caused by either sudden space-occupying intraorbital lesions, including retrobulbar hemorrhage (RBH), or direct damage to the prechiasmatic pathway. Contrary to traumatic optic neuropathy, RBH must be diagnosed and treated immediately to prevent permanent damage to the visual system. Therefore, monitoring and handling of visual pathway damage are mandatory. Flash visual evoked potentials and electroretinograms can provide evidence of the status of conductivity of the visual pathway when clinical assessment is not feasible. Both are thus essential diagnostic procedures not only for primary diagnosis but also for intraoperative evaluation. In case of RBH surgical decompression is compulsory. However, traumatic optic neuropathy does not respond to either corticosteroids or optic canal surgery. Modern craniomaxillofacial surgery requires detailed consideration of the diagnosis and treatment of traumatic visual pathway damage with the ultimate goal of preserving visual acuity.

Ciliary neurotrophic factor (CNTF)-mediated ganglion cell survival in a rodent model of non-arteritic anterior ischaemic optic neuropathy (NAION)

BackgroundCiliary neurotrophic factor (CNTF) has been shown to protect retinal ganglion cells (RGCs) in traumatic optic nerve injury. We sought to evaluate this neuroprotective effect of CNTF after an ischaemic...

Protection of pattern electroretinogram and retinal ganglion cells by oncostatin M after optic nerve injury.

Injury to retinal ganglion cell (RGC) axons leads to selective loss of RGCs and vision. Previous studies have shown that exogenous neurotrophic factors promote RGC survival. We investigated the neuroprotective effects of oncostatin M (OSM), a member of the IL-6 family of cytokines, on pattern electroretinogram (PERG) and RGC survival after optic nerve crush (ON-crush) in the mouse. BALB/C mice received ON-crush in the left eyes for either 4-second or 1-second duration (4-s or 1-s). Fluoro-gold retrograde labeling was used to identify RGCs. RGC function was assessed by PERG measurement. OSM or CNTF protein was injected intravitreally immediately after ON-crush. OSM responsive cells were identified by localization of increased STAT3 phosphorylation. Significant higher RGC survival (46% of untreated control) was seen in OSM-treated eyes when assessed 2 weeks after 4-s ON-crush as compared to that (14% of untreated control) of the PBS-treated eyes (P<0.001). In addition, PERG amplitude was significantly higher in eyes treated with OSM or CNTF 1 week after 1-s ON-crush (36% of baseline) as compared with the amplitude of PBS-treated eyes (19% of the baseline, P = 0.003). An increase in STAT3 phosphorylation was localized in Müller layer after OSM treatment, suggesting that Müller cells mediate the effect of OSM. Our results demonstrate that one single injection of either OSM or CNTF after ON-crush improves RGC survival together with their electrophysiological activity. These data provide proof-of-concept for using neurotrophic factors OSM and CNTF for RGC degenerative diseases, including glaucoma and acute optic nerve trauma.

Bilateral traumatic optic nerve avulsion in a Thoroughbred gelding

SummaryThis report describes an unusual case of acute blindness following traumatic head injury in a mature horse. The horse fell over backwards and subsequently presented with bilateral blindness and epistaxis. Vision did not return following medical supportive therapy and euthanasia was elected. Post mortem findings revealed a basisphenoid fracture and bilateral optic nerve avulsion rostral to the optic chiasm, an uncommon presentation of traumatic blindness not previously reported in the horse.

Traumatic Optic Neuropathy and Second Optic Nerve Injuries

Current controversy about the primary treatment of traumatic optic neuropathy (TON) has anchored on final vision following injury, but, to our knowledge, no study has examined the effect of different treatments on regaining and protecting optic nerve reserve or on the outcome of second optic nerve injuries. To assess vision improvement in patients treated by various methods who have a second incidence of TON. Retrospective medical record review of 12 patients with a second TON seen in an 18-year period (mean follow-up, 11.3 months) at a single tertiary care oculoplastic practice. Observation, high-dose corticosteroids, optic nerve decompression, or high-dose corticosteroids plus optic nerve decompression. Change in vision on the Snellen eye chart. RESULTS All second TON events involved the same-side optic nerve as initially injured, and with observation alone, corticosteroids, or corticosteroids and partial optic canal decompression, all patients had vision improvement after their initial injury (P = .004). However, following the second optic nerve injury, most patients' vision fell to the pretreatment level of the first injury, and subsequent management of the second injury with corticosteroids and/or optic canal decompression provided little or no vision return (P = .05). In contrast, optic canal decompressions performed for 91 primary TON injuries resulted in 82.4% having some degree of vision improvement. Patients with TON may have a second optic nerve insult, and vision recovery from the second event may be limited regardless of primary treatment choice.

Ocular manifestations of head injury and incidence of post-traumatic ocular motor nerve involvement in cases of head injury: a clinical review

As the eyes are in close proximity to the skull, they can get simultaneously affected in head injuries. This close association warrants careful ocular examination in all cases of head injury. This is a prospective non-randomized analytical study to evaluate various ocular manifestations in cases of head injury with special reference to ocular motor nerve involvement, correlation between pupillary changes, and survival. A total of 1,184 patients with head injury were screened for ocular manifestations. This study comprises 594 patients with ocular manifestations of head injury. All the relevant data was compiled and analyzed as per proforma. Ocular manifestations were evaluated in each patient and appropriate investigations were carried out. Patients with ocular morbidity were analyzed for age, sex, mode of injury, Glasgow Coma Score, and associated injuries in addition to ophthalmic and neurosurgical evaluations. Of the 594 patients, 81.6 % were male and 18.4 % were female, with a male-to-female ratio of 4:1. The major cause of head injury was road traffic accidents (70.37 %). The most common age group involved was, 21-40-year-olds (67.40 %). Out of 594 patients, ecchymosis was found in 51.85 %, subconjunctival hemorrhage in 44.44 %, lid edema in 41.48 %, lacerated wound in 22.59 %, pupillary involvement in 21.04 %, ptosis in 6.73 %, cranial nerve palsy in 11.62 %, orbital fractures in 10.44 %, optic nerve trauma in 4.04 %, and exposure keratitis in 4.21 %. Patients with bilaterally dilated or pinpoint fixed pupils had a 10 times higher risk of mortality than patients without pupillary involvement. Third nerve involvement was seen 2.85 times more frequently in frontal and parietal region injuries compared to other sites of injury. The involvement of the sixth nerve occurred 4.6 times more frequently in parietal region injuries compared to other sites of injury.

BDNF Treatment and Extended Recovery From Optic Nerve Trauma in the Cat

We examined the treatment period necessary to restore retinal and visual stability following trauma to the optic nerve. Cats received unilateral optic nerve crush and no treatment (NT), treatment of the injured eye with brain-derived neurotrophic factor (BDNF), or treatment of the injured eye combined with treatment of visual cortex for 2 or 4 weeks. After 1-, 2-, 4-, or 6-week survival periods, pattern electroretinograms (PERGs) were obtained and retinal ganglion cell (RGC) survival determined. In the peripheral retina, RGC survival for NT, eye only, and eye + cortex animals was 55%, 78%, and 92%, respectively, at 1 week, and 31%, 60%, and 93%, respectively, at 2 weeks. PERGs showed a similar pattern of improvement. After 4 weeks, RGC survival was 7%, 29%, and 53% in each group, with PERGs in the dual-treated animals similar to the 1- to 2-week animals. For area centralis (AC), the NT, eye only, and eye + cortex animals showed 47%, 78%, and 82% survival, respectively, at 2 weeks, and 13%, 54%, and 81% survival, respectively, at 4 weeks. Removing the pumps at 2 weeks resulted in ganglion cell survival levels of 76% and 74% in the AC at 4 and 6 weeks postcrush, respectively. The PERGs from 2-week treated, but 4- and 6-week survival animals were comparable to those of the 2-week animals. Treating the entire central visual pathway is important following optic nerve trauma. Long-term preservation of central vision may be achieved with as little as 2 weeks of treatment using this approach.

Engrafted Human Induced Pluripotent Stem Cell-Derived Anterior Specified Neural Progenitors Protect the Rat Crushed Optic Nerve

BackgroundDegeneration of retinal ganglion cells (RGCs) is a common occurrence in several eye diseases. This study examined the functional improvement and protection of host RGCs in addition to the survival, integration and neuronal differentiation capabilities of anterior specified neural progenitors (NPs) following intravitreal transplantation.Methodology/Principal FindingsNPs were produced under defined conditions from human induced pluripotent stem cells (hiPSCs) and transplanted into rats whose optic nerves have been crushed (ONC). hiPSCs were induced to differentiate into anterior specified NPs by the use of Noggin and retinoic acid. The hiPSC-NPs were labeled by green fluorescent protein or a fluorescent tracer 1,1′ -dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) and injected two days after induction of ONC in hooded rats. Functional analysis according to visual evoked potential recordings showed significant amplitude recovery in animals transplanted with hiPSC-NPs. Retrograde labeling by an intra-collicular DiI injection showed significantly higher numbers of RGCs and spared axons in ONC rats treated with hiPSC-NPs or their conditioned medium (CM). The analysis of CM of hiPSC-NPs showed the secretion of ciliary neurotrophic factor, basic fibroblast growth factor, and insulin-like growth factor. Optic nerve of cell transplanted groups also had increased GAP43 immunoreactivity and myelin staining by FluoroMyelin™ which imply for protection of axons and myelin. At 60 days post-transplantation hiPSC-NPs were integrated into the ganglion cell layer of the retina and expressed neuronal markers.Conclusions/SignificanceThe transplantation of anterior specified NPs may improve optic nerve injury through neuroprotection and differentiation into neuronal lineages. These NPs possibly provide a promising new therapeutic approach for traumatic optic nerve injuries and loss of RGCs caused by other diseases.

SIRT1 Promotes RGC Survival and Delays Loss of Function Following Optic Nerve Crush

Activation of SIRT1 deacetylase prevents retinal ganglion cell (RGC) loss in experimental optic neuritis, an inflammatory optic neuropathy. While mechanisms of this effect are not known, evidence suggests it involves reduction of oxidative stress. We hypothesized that SIRT1 reduces RGC loss due to oxidative stress in noninflammatory optic neuropathies, and examined effects following traumatic injury. Optic nerve crush injury was induced in wild-type C57BL/6 mice, mice overexpressing SIRT1, and mice with conditional deletion of SIRT1 in neurons. Wild-type mice were treated daily with vehicle or 250 mg/kg resveratrol, a naturally occurring polyphenol that activates SIRT1. RGC function was assessed by pupillometry and optokinetic responses (OKR), and RGC survival was measured. Superoxide levels were measured to assess oxidative stress. Significant decreases in pupillary light responses, OKR and RGC survival occurred 1 week after optic nerve crush, with progressive worsening at 2 to 4 weeks. Resveratrol treatment and SIRT1 overexpression delayed RGC loss and loss of pupillary light responses following optic nerve crush, although no change in RGC loss occurred in neuronal SIRT1-deficient mice. A significant accumulation of superoxide was detected in wild-type optic nerves following crush, and was reduced in mice overexpressing SIRT1 or treated with resveratrol. SIRT1 delays RGC loss following traumatic injury. Effects are associated with reduced oxidative stress. Results suggest SIRT1-activating drugs may have a specific role in preventing traumatic optic nerve damage, and suggest a broader role for this strategy in treating a variety of optic neuropathies that may include a component of oxidative stress.

Transcorneal electrical stimulation alters morphology and survival of retinal ganglion cells after optic nerve damage

Traumatic optic nerve injury leads to retrograde death of retinal ganglion cells (RGCs), but transcorneal electrical stimulation (TES) can increase the cell survival rate. To understand the mechanisms and to further define the TES-induced effects we monitored in living animals RGC morphology and survival after optic nerve crush (ONC) in real time by using in vivo confocal neuroimaging (ICON) of the retina.ONC was performed in rats and ICON was performed before crush and on post-lesion days 3, 7 and 15 which allowed us to repeatedly record RGC number and size. TES or sham-stimulation were performed immediately after the crush and on post-injury day 11.Three days after ONC we detected a higher percentage of surviving RGCs in the TES group as compared to sham-treated controls. However, the difference was below significance level on day 7 and disappeared completely by day 15. The death rate was more variable amongst the TES-treated rats than in the control group. Morphological analysis revealed that average cell size changed significantly in the control group but not in stimulated animals and the morphological alterations of surviving neurons were smaller in TES-treated compared to control cells.In conclusion, TES delays post-traumatic cell death significantly. Moreover, we found “responder animals” which also benefited in the long-term from the treatment. Our in vivo cellular imaging results provide evidence that TES reduces ONC-associated neuronal swelling and shrinkage especially in RGCs which survived long-term. Further studies are now needed to determine the differences of responders vs. non-responders.

Electroretinographical and histological study of mouse retina after optic nerve section: a comparison between wild‐type and retinal degeneration 1 mice

Retinal ganglion cell death underlies the pathophysiology of neurodegenerative disorders such as glaucoma or optic nerve trauma. To assess the potential influence of photoreceptor degeneration on retinal ganglion cell survival, and to evaluate functionality, we took advantage of the optic nerve section mouse model. Surviving retinal ganglion cells were double-stained by exposing both superior colliculi to fluorogold, and by applying dextran-tetramethylrhodamine to the injured optic nerve stump. To assess retinal function in wild-type animals, electroretinograms were recorded on the injured eyes and compared with the contralateral. Similar labelling experiments were carried out on retinal degeneration 1 mice. Surviving retinal ganglion cells were counted 21 days after axotomy and compared with wild-type mice. No functional experiments were performed on retinal degeneration 1 animals because they do not develop normal electroretinographical responses. A significant decrease in retinal ganglion cell density was observed 6 days after axotomy in the wild type. Functional studies revealed that, in scotopic conditions, axotomy induced a significant amplitude decrease in the positive scotopic threshold response component of the electroretinogram. Such decrease paralleled cell loss, suggesting it may be an appropriate technique to evaluate functionality. When comparing retinal ganglion cell densities in wild-type and retinal degeneration 1 mice, a significant greater survival was observed on the latter. After optic nerve section, electroretinographical recordings exhibited a progressive decrease in the amplitude of the positive scotopic threshold response wave, reflecting ganglion cell loss. Interestingly, rod degeneration seemed, at least initially, to protect from axotomy-driven damage.

Blunt Facial Trauma Causing Isolated Optic Nerve Hematoma

Traumatic optic neuropathy is an uncommon, yet serious, result of facial trauma. The authors present a novel case of a 59-year-old gentleman who presented with an isolated blunt traumatic left optic nerve hematoma causing vision loss. There were no other injuries or fractures to report. This case highlights the importance of early recognition of this rare injury and reviews the current literature and management of traumatic optic neuropathy.

Endoscopic endonasal skull base surgery in the pediatric population

The use of endoscopic endonasal surgery (EES) for skull base pathologies in the pediatric population presents unique challenges and has not been well described. The authors reviewed their experience with endoscopic endonasal approaches in pediatric skull base surgery to assess surgical outcomes and complications in the context of presenting patient demographics and pathologies. A retrospective review of 133 pediatric patients who underwent EES at our institution from July 1999 to May 2011 was performed. A total of 171 EESs were performed for skull base tumors in 112 patients and bony lesions in 21. Eighty-five patients (63.9%) were male, and the mean age at the time of surgery was 12.7 years (range 2.3-18.0 years). Skull base tumors included angiofibromas (n = 24), craniopharyngiomas (n = 16), Rathke cleft cysts (n = 12), pituitary adenomas (n = 11), chordomas/chondrosarcomas (n = 10), dermoid/epidermoid tumors (n = 9), and 30 other pathologies. In total, 19 tumors were malignant (17.0%). Among patients with follow-up data, gross-total resection was achieved in 16 cases of angiofibromas (76.2%), 9 of craniopharyngiomas (56.2%), 8 of Rathke cleft cysts (72.7%), 7 of pituitary adenomas (70%), 5 of chordomas/chondrosarcomas (50%), 6 of dermoid/epidermoid tumors (85.7%), and 9 cases of other pathologies (31%). Fourteen patients received adjuvant radiotherapy, and 5 received chemotherapy. Sixteen patients (15.4%) showed tumor recurrence and underwent reoperation. Bony abnormalities included skull base defects (n = 12), basilar invagination (n = 4), optic nerve compression (n = 3) and trauma (n = 2); preexisting neurological dysfunction resolved in 12 patients (57.1%), improved in 7 (33.3%), and remained unchanged in 2 (9.5%). Overall, complications included CSF leak in 14 cases (10.5%), meningitis in 5 (3.8%), transient diabetes insipidus in 8 patients (6.0%), and permanent diabetes insipidus in 12 (9.0%). Five patients (3.8%) had transient and 3 (2.3%) had permanent cranial nerve palsies. The mean follow-up time was 22.7 months (range 1-122 months); 5 patients were lost to follow-up. Endoscopic endonasal surgery has proved to be a safe and feasible approach for the management of a variety of pediatric skull base pathologies. When appropriately indicated, EES may achieve optimal outcomes in the pediatric population.

Towards Retinal Ganglion Cell Regeneration

Traumatic optic nerve injury and glaucoma are among the leading causes of incurable vision loss across the world. What is worse, neither pharmacological nor surgical interventions are significantly effective in reversing or halting the progression of vision loss. Advances in cell biology offer some hope for the victims of optic nerve damage and subsequent partial or complete visual loss. Retinal ganglion cells (RGCs) travel through the optic nerve and carry all visual signals to the brain. After injury, RGC axons usually fail to regrow and die, leading to irreversible loss of vision. Various kinds of cells and factors possess the ability to support the process of axon regeneration for RGCs. This article summarizes the latest advances in RGC regeneration.

Effect of PACAP in central and peripheral nerve injuries.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a bioactive peptide with diverse effects in the nervous system. In addition to its more classic role as a neuromodulator, PACAP functions as a neurotrophic factor. Several neurotrophic factors have been shown to play an important role in the endogenous response following both cerebral ischemia and traumatic brain injury and to be effective when given exogenously. A number of studies have shown the neuroprotective effect of PACAP in different models of ischemia, neurodegenerative diseases and retinal degeneration. The aim of this review is to summarize the findings on the neuroprotective potential of PACAP in models of different traumatic nerve injuries. Expression of endogenous PACAP and its specific PAC1 receptor is elevated in different parts of the central and peripheral nervous system after traumatic injuries. Some experiments demonstrate the protective effect of exogenous PACAP treatment in different traumatic brain injury models, in facial nerve and optic nerve trauma. The upregulation of endogenous PACAP and its receptors and the protective effect of exogenous PACAP after different central and peripheral nerve injuries show the important function of PACAP in neuronal regeneration indicating that PACAP may also be a promising therapeutic agent in injuries of the nervous system.

Protective effect of ciliary neurotrophic factor on retinal ganglion cell in acute ocular hypertension rat

Background Glaucoma associates with apoptosis of retinal ganglion cells ( RGCs).Research showed that ciliary neurotrophic factor (CNTF) can repair optic nerve trauma,but it has not reported whether CNTF has a protective effect on glaucomatous optic neuropathy. Objective This experimental study was to explore the protective effect of CNTF on RGCs in rat eyes with acute ocular hypertension. Methods Ocular acute hypertension models were induced in bilateral eyes of 24 clean Wistar rats by forced perfusion of a balanced salt solution into the anterior chamber.Two days before molding,0.5 μg recombinant human CNTF (5 μl) was injected intravitreously in the left eyes,and 5 mmol/L sodium phosphate solution (5 μl) was injected in the same way as the control group.Three other Wistar rats were used as the normal control group.The animals were sacrificed by excessive anesthesia and the retinal sections were prepared 1,3,7,14 days after molding.The morphology of the retina was examined and RGCs counting was performed by hematoxylin & eosin staining and observed under a light microscope.The expression of glutamic acid in RGCs was assessed by immunochemistry. Results Regular retinal structure with clearly defined cell layers were observed in normal control rats.Changes in vacuoles in RGCs were seen in the model control group.The number of degenerative RGCs decreased in the CNTF group.Compared with the model control group,number of normal RGCs increased from 1 day to 14 days after molding with a significant difference between the two groups (all P=0.000).Immunochemistry assay showed that the numbers of positive cells for glutamic acid were 5.50±1.04 and 6.00±1.41 for the average of 3 fields at 3 days or 7 days in the CNTF group,and those in the model control group were 9.00±2.91 and 10.83 ± 1.94,respectively,showing significant differences between them ( all P =0.000 ).However,no comparable differences were found in the numbers of positive cells for glutamic acid at 1 day and 14 days between the two groups( P=0.578,0.180). Conclusions CNTF down-regulates the expression of glutamic acid in RGCs and offers neuroprotection for RGCs in an acute glaucoma rat model. Key words: Ciliary neurotrophie factor; Ocular hypertention; Retinal ganglion cell; Glutamic acid

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist inhibits apoptosis of retinal ganglion cells in a rabbit model of optic nerve injury.

A rabbit model of traumatic optic nerve injury, established by occlusion of the optic nerve using a vascular clamp, was used to investigate the effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist GYKI 52466 on apoptosis of retinal ganglion cells following nerve injury. Hematoxylin-eosin staining and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that retinal ganglion cells gradually decreased with increasing time of optic nerve injury, while GYKI 52466 could inhibit this process. The results demonstrate that following acute optic nerve injury, apoptosis of retinal ganglion cells is a programmed process, which can be inhibited by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist.