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1.
Proc Natl Acad Sci U S A ; 119(10): e2115973119, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35235463

RESUMO

White matter disorders of the central nervous system (CNS), such as multiple sclerosis (MS), lead to failure of nerve conduction and long-lasting neurological disabilities affecting a variety of sensory and motor systems, including vision. While most disease-modifying therapies target the immune and inflammatory response, the promotion of remyelination has become a new therapeutic avenue to prevent neuronal degeneration and promote recovery. Most of these strategies have been developed in short-lived rodent models of demyelination, which spontaneously repair and do not reflect the size, organization, and biology of the human CNS. Thus, well-defined nonhuman primate models are required to efficiently advance therapeutic approaches for patients. Here, we followed the consequence of long-term toxin-induced demyelination of the macaque optic nerve on remyelination and axon preservation, as well as its impact on visual functions. Findings from oculomotor behavior, ophthalmic examination, electrophysiology, and retinal imaging indicate visual impairment involving the optic nerve and retina. These visual dysfunctions fully correlated at the anatomical level, with sustained optic nerve demyelination, axonal degeneration, and alterations of the inner retinal layers. This nonhuman primate model of chronic optic nerve demyelination associated with axonal degeneration and visual dysfunction, recapitulates several key features of MS lesions and should be instrumental in providing the missing link to translate emerging repair promyelinating/neuroprotective therapies to the clinic for myelin disorders, such as MS.


Assuntos
Axônios , Nervo Óptico/patologia , Remielinização , Retina/patologia , Transtornos da Visão/patologia , Animais , Modelos Animais de Doenças , Potenciais Evocados Visuais , Macaca fascicularis , Masculino , Esclerose Múltipla/patologia , Reflexo Pupilar , Retina/diagnóstico por imagem , Retina/fisiopatologia , Tomografia de Coerência Óptica
2.
Vet Sci ; 9(2)2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35202302

RESUMO

We tested 144 pet rabbits sampled in France between November 2020 and June 2021 for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by microsphere immunoassay. We reported the first evidence of a natural SARS-CoV-2 infection in rabbits with a low observed seroprevalence between 0.7% and 1.4%.

3.
Vet Med Sci ; 8(1): 14-20, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34704394

RESUMO

Although there are several reports in the literature of SARS-CoV-2 infection in cats, few SARS-CoV-2 sequences from infected cats have been published. In this study, SARS-CoV-2 infection was evaluated in two cats by clinical observation, molecular biology (qPCR and NGS), and serology (microsphere immunoassay and seroneutralization). Following the observation of symptomatic SARS-CoV-2 infection in two cats, infection status was confirmed by RT-qPCR and, in one cat, serological analysis for antibodies against N-protein and S-protein, as well as neutralizing antibodies. Comparative analysis of five SARS-CoV-2 sequence fragments obtained from one of the cats showed that this infection was not with one of the three recently emerged variants of SARS-CoV-2. This study provides additional information on the clinical, molecular, and serological aspects of SARS-CoV-2 infection in cats.


Assuntos
COVID-19 , Doenças do Gato , Animais , COVID-19/veterinária , Doenças do Gato/epidemiologia , Gatos , França/epidemiologia , Pandemias , SARS-CoV-2
4.
One Health ; 11: 100192, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33169106

RESUMO

In a survey of household cats and dogs of laboratory-confirmed COVID-19 patients, we found a high seroprevalence of SARS-CoV-2 antibodies, ranging from 21% to 53%, depending on the positivity criteria chosen. Seropositivity was significantly greater among pets from COVID-19+ households compared to those with owners of unknown status. Our results highlight the potential role of pets in the spread of the epidemic.

5.
Biomed Hub ; 3(2): 1-11, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31988957

RESUMO

PURPOSE: The present study aimed to assess functional and structural benefits of erythropoietin (EPO) when administered subconjunctivally in the retina of glaucomatous rats using electroretinography (ERG) and retinal thickness (RT) measurements. METHODS: Glaucoma was experimentally induced in 26 Wistar Hannover albino rats. Animals were divided into 2 groups of 13 animals each: a treated group receiving a unique subconjunctival injection of 1,000 IU of EPO and a control group receiving a saline solution. In each group, 7 animals were used for retinal function evaluation (ERG) and 6 animals were used for retinal structural evaluation (histology). RT was measured, dorsally and ventrally, at 500 µm (RT1) and at 1,500 µm (RT2) from the optic nerve. RESULTS: Retinal function evaluation: for both scotopic and photopic conditions, ERG wave amplitudes increased in the treated group. This increase was statistically significant (p < 0.05) in photopic conditions. Structural evaluation: for both locations RT1 and RT2, the retinas were significantly (p < 0.05) thicker in the treated group. CONCLUSION: Subconjunctival EPO administration showed beneficial effects both on retinal structure and on retinal function in induced glaucoma in albino rats. This neuroprotective effect should be applied in other animal species.

6.
Transl Res ; 188: 40-57.e4, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28754419

RESUMO

Several approaches have been developed for gene therapy in RPE65-related Leber congenital amaurosis. To date, strategies that have reached the clinical stages rely on adeno-associated viral vectors and two of them documented limited long-term effect. We have developed a lentiviral-based strategy of RPE65 gene transfer that efficiently restored protein expression and cone function in RPE65-deficient mice. In this study, we evaluated the ocular and systemic tolerances of this lentiviral-based therapy (LV-RPE65) on healthy nonhuman primates (NHPs), without adjuvant systemic anti-inflammatory prophylaxis. For the first time, we describe the early kinetics of retinal detachment at 2, 4, and 7 days after subretinal injection using multimodal imaging in 5 NHPs. We revealed prolonged reattachment times in LV-RPE65-injected eyes compared to vehicle-injected eyes. Low- (n = 2) and high-dose (n = 2) LV-RPE65-injected eyes presented a reduction of the outer nuclear and photoreceptor outer segment layer thickness in the macula, that was more pronounced than in vehicle-injected eyes (n = 4). All LV-RPE65-injected eyes showed an initial perivascular reaction that resolved spontaneously within 14 days. Despite foveal structural changes, full-field electroretinography indicated that the overall retinal function was preserved over time and immunohistochemistry identified no difference in glial, microglial, or leucocyte ocular activation between low-dose, high-dose, and vehicle-injected eyes. Moreover, LV-RPE65-injected animals did not show signs of vector shedding or extraocular targeting, confirming the safe ocular restriction of the vector. Our results evidence a limited ocular tolerance to LV-RPE65 after subretinal injection without adjuvant anti-inflammatory prophylaxis, with complications linked to this route of administration necessitating to block this transient inflammatory event.


Assuntos
Proteínas do Olho/administração & dosagem , Técnicas de Transferência de Genes , Vetores Genéticos/administração & dosagem , Vetores Genéticos/efeitos adversos , Lentivirus/genética , Receptores Acoplados a Proteínas G/administração & dosagem , Animais , Feminino , Macaca fascicularis , Retina
7.
Vet Ophthalmol ; 18(6): 510-4, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25623165

RESUMO

A 3-month wild rabbit was presented for examination of ocular opacities in the left eye. A complete bilateral ocular examination including slit-lamp examination, indirect ophthalmoscopy, tonometry, and ultrasound biomicroscopy was performed. Biomicroscopy of the lens of the left eye showed a retrolental fibrovascular membrane causing leukocoria. The opacity prevented biomicroscopy of the vitreous and funduscopy OS. No other disorder was present in either eye. Ultrasound examination did not show any difference between the right and left eye. Histopathological examination showed a 50-µm thick, preretinal, retrolental, nonpigmented, fibrovascular tissue. Posterior synechiae were present, but no other lesion of the posterior segment was found in this eye. These ocular abnormalities are consistent with a persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous (PHTVL/PHPV), similar to those described in other species.


Assuntos
Vítreo Primário Hiperplásico Persistente/veterinária , Coelhos/anormalidades , Corpo Vítreo/anormalidades , Animais , Feminino , Vítreo Primário Hiperplásico Persistente/diagnóstico , Vítreo Primário Hiperplásico Persistente/patologia , Corpo Vítreo/patologia
8.
Exp Toxicol Pathol ; 67(1): 13-20, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25446799

RESUMO

The overall purpose of this study was to establish a model that may be used for examining the effect of Vigabatrin-induced retinal toxicity in pigmented rats, and subsequently examine the possible effects of taurine on the retinal toxicity. In the first part of the study, pigmented Long Evans rats were subjected to combinations of induced mydriasis, low/high light intensities (40/2000 lx) and oral administration of near-MTD (Maximum Tolerated Dose) doses (200 mg/kg/day) of Vigabatrin for up to 6 weeks. The combination of mydriasis and high light intensity applied to Long Evans rats resulted in retinal damage that was increased by the administration of Vigabatrin. In the second part of the study Long Evans rats were subjected to combinations of induced mydriasis and high/low light intensity (40/2000 lx) while being orally administered low (30 mg/kg/day) or high (200 mg/kg/day) doses of Vigabatrin for up to 6 weeks. In addition, selected groups of animals were administered taurine via the drinking water (20 mg/ml), resulting in systemic taurine concentrations of approximately threefold the endogenous concentration. The combined results of the studies demonstrate that retinal damage can be induced in pigmented animals when combining mydriasis and high light intensity. Retinal damage was functionally evaluated by electroretinography (ERG), then confirmed by histopathology. While depending on mydriasis and high light intensity, administration of Vigabatrin increased the retinal toxicity and resulted in the formation of rosette-like structures in the retina in a dose-related manner. Administration of taurine did not alleviate the Vigabatrin-induced retinal toxicity, as demonstrated either functionally by ERG or morphologically, although systemic concentrations of 3-fold the endogenous levels were reached, and it was thus not possible to demonstrate a protective effect of taurine in these pigmented animals.


Assuntos
Anticonvulsivantes/toxicidade , Retina/efeitos dos fármacos , Retina/patologia , Taurina/toxicidade , Vigabatrina/toxicidade , Animais , Atropina/toxicidade , Modelos Animais de Doenças , Eletrorretinografia , Masculino , Midríase/patologia , Midriáticos/toxicidade , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley
9.
PLoS One ; 9(11): e111873, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25380252

RESUMO

In both humans and dogs, the primary risk factor for glaucoma is high intraocular pressure (IOP), which may be caused by iridocorneal angle (ICA) abnormalities. Oxidative stress has also been implicated in retinal ganglion cell damage associated with glaucoma. A suspected inherited form of glaucoma was recently identified in Eurasier dogs (EDs), a breed for which pedigrees are readily available. Because of difficulties in assessing ICA morphology in dogs with advanced glaucoma, we selected a cohort of apparently healthy dogsfor the investigation of ICA morphological status, IOP and plasma concentrations of oxidative stress biomarkers. We aimed to establish correlations between these factors, to identify predictive markers of glaucoma in this dog breed. A cohort of 28 subjects, volunteered for inclusion by their owners, was selected by veterinary surgeons. These dogs were assigned to four groups: young males, young females (1-3 years old), adult males and adult females (4-8 years old). Ocular examination included ophthalmoscopy, tonometry, gonioscopy, biometry and ultrasound biomicroscopy (UBM), and the evaluation of oxidative stress biomarkers consisting of measurements of plasma glutathione peroxidase (GP) activity and taurine and metabolic precursor (methionine and cysteine) concentrations in plasma. The prevalence of pectinate ligament abnormalities was significantly higher in adult EDs than in young dogs. Moreover, in adult females, high IOP was significantly correlated with a short axial globe length, and a particularly large distance between Schwalbe's line and the anterior lens capsule. GP activity levels were significantly lower in EDs than in a randomized control group of dogs, and plasma taurine concentrations were higher. Hence, ICA abnormalities were associated with weaker antioxidant defenses in EDs, potentially counteracted by higher plasma taurine concentrations. This study suggests that EDs may constitute an appropriate canine model for the development of glaucoma. This cohort will be used as a sentinel for longitudinal monitoring.


Assuntos
Biometria , Glaucoma/diagnóstico , Saúde , Animais , Estudos de Coortes , Suscetibilidade a Doenças , Cães , Feminino , Glaucoma/diagnóstico por imagem , Glaucoma/metabolismo , Glaucoma/fisiopatologia , Gonioscopia , Pressão Intraocular , Masculino , Manometria , Ultrassonografia
10.
Prog Retin Eye Res ; 41: 44-63, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24721186

RESUMO

Taurine is the most abundant amino acid in the retina. In the 1970s, it was thought to be involved in retinal diseases with photoreceptor degeneration, because cats on a taurine-free diet presented photoreceptor loss. However, with the exception of its introduction into baby milk and parenteral nutrition, taurine has not yet been incorporated into any commercial treatment with the aim of slowing photoreceptor degeneration. Our recent discovery that taurine depletion is involved in the retinal toxicity of the antiepileptic drug vigabatrin has returned taurine to the limelight in the field of neuroprotection. However, although the retinal toxicity of vigabatrin principally involves a deleterious effect on photoreceptors, retinal ganglion cells (RGCs) are also affected. These findings led us to investigate the possible role of taurine depletion in retinal diseases with RGC degeneration, such as glaucoma and diabetic retinopathy. The major antioxidant properties of taurine may influence disease processes. In addition, the efficacy of taurine is dependent on its uptake into retinal cells, microvascular endothelial cells and the retinal pigment epithelium. Disturbances of retinal vascular perfusion in these retinal diseases may therefore affect the retinal uptake of taurine, resulting in local depletion. The low plasma taurine concentrations observed in diabetic patients may further enhance such local decreases in taurine concentration. We here review the evidence for a role of taurine in retinal ganglion cell survival and studies suggesting that this compound may be involved in the pathophysiology of glaucoma or diabetic retinopathy. Along with other antioxidant molecules, taurine should therefore be seriously reconsidered as a potential treatment for such retinal diseases.


Assuntos
Degeneração Retiniana/prevenção & controle , Taurina/fisiologia , Animais , Humanos , Fármacos Neuroprotetores/uso terapêutico , Degeneração Retiniana/fisiopatologia , Taurina/química , Taurina/uso terapêutico
11.
Neurosci Lett ; 543: 78-83, 2013 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-23562505

RESUMO

Melatonin follows a circadian rhythm entrained by the light/dark cycle and plays a role in promoting light sensitivity at night. It has been suggested that melatonin and dopamine reciprocal inhibition may contribute to the switch between day and night vision. The purpose of this study was to investigate the impact of a high dose of melatonin administration on the photopic and scotopic electroretinogram (ERG) of dogs in the daytime, when it is not thought to be present. Photopic and scotopic ERG luminance response functions were obtained from 7 anaesthetized beagle dogs (3 males and 4 females), once without melatonin (control) and once after oral administration of melatonin (90 mg/dog). Vmax (maximal b-wave amplitude achieved) and logK (retinal sensitivity) were calculated from the derived luminance response function. Photopic flicker ERG was also recorded. In photopic condition, a-wave amplitude (control: -126.90 µV; with melatonin: -49.64 µV; p<0.001) and Vmax (control: 252.50 µV; with melatonin: 115.40 µV; p<0.001) were decreased. A significant reduction of the photopic flicker ERG amplitude was observed after melatonin ingestion. In scotopic condition, an overall difference was reported before and after melatonin ingestion for the a- and b-wave amplitude, but no change was significant for Vmax. Melatonin ingestion at a high dose during the day decreases the photopic amplitude of a- and b-wave, but has no impact on implicit time. This negative impact of melatonin on photopic system may serve to promote night vision.


Assuntos
Luz , Melatonina/farmacologia , Células Fotorreceptoras Retinianas Bastonetes/efeitos dos fármacos , Administração Oral , Animais , Ritmo Circadiano , Escuridão , Cães , Eletrorretinografia , Feminino , Masculino , Melatonina/administração & dosagem , Visão Noturna/efeitos dos fármacos , Células Fotorreceptoras Retinianas Bastonetes/fisiologia
12.
Toxicology ; 308: 50-9, 2013 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-23567313

RESUMO

Retinal toxicity of chloroquine has been known for several years, but the mechanism(s) of toxicity remain controversial; some author support the idea that the binding of chloroquine to melanin pigments in the retinal pigmented epithelium (RPE) play a major toxic role by concentrating the drug in the eye. In our study, 12 albinos Sprague-Dawley (SD) and 12 pigmented Brown Norway (BN) rats were treated orally for 3 months with chloroquine to compare functional and pathological findings. On Flash electroretinograms (ERG) performed in scotopic conditions, similar and progressive (time-dependent) delayed onset and decreased amplitudes of oscillatory potentials (from Day 71) and b-waves (on Day 92) were identified in both BN and SD rats. In both strains, identical morphological changes consisted of neuronal phospholipidosis associated with UV auto-fluorescence without evidence of retinal degeneration and gliosis; the RPE did not show any morphological lesions or autofluorescence. IHC analyses demonstrated a decrease in GABA expression in the inner nuclear layer. In addition, a marked accumulation of synaptic vesicles coupled with a marked disruption of neurofilaments in the optic nerve fibers was identified. In conclusion, ERG observations were very similar to those described in humans. Comparable ERG modifications, histopathology and immunohistochemistry findings were observed in the retina of both rat strains suggesting that melanin pigment is unlikely involved. chloroquine-induced impairment of synaptic vesicle transport, likely related to disruption of neurofilaments was identified and non-previously reported. This new mechanism of toxicity may also be responsible for the burry vision described in humans chronically treated with chloroquine.


Assuntos
Cloroquina/toxicidade , Neurônios/metabolismo , Fosfolipídeos/metabolismo , Retina/metabolismo , Vesículas Sinápticas/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/fisiologia , Eletrorretinografia/métodos , Masculino , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos , Ratos Endogâmicos BN , Ratos Sprague-Dawley , Retina/efeitos dos fármacos , Retina/patologia , Especificidade da Espécie , Vesículas Sinápticas/efeitos dos fármacos , Vesículas Sinápticas/patologia
13.
Adv Exp Med Biol ; 775: 145-54, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23392931

RESUMO

In the 70s, the amino acid taurine was found essential for photoreceptor survival. Recently, we found that taurine depletion can also trigger retinal ganglion cell degeneration both in vitro and in vivo. Therefore, evaluation of taurine levels could be a crucial biomarker for different pathologies of retinal ganglion cells such as glaucoma. Because different breeds of dog can develop glaucoma, we performed taurine measurements on plasma and aqueous humour samples from pet dogs. Here, we exposed results from a pilot study on normal selected breed of pet dogs, without any ocular pathology. Samples were collected by veterinarians who belong to the Réseau Européen d'Ophtalmologie Vétérinaire et de Vision Animale. Following measurements by high-performance liquid chromatography (HPLC), the averaged taurine concentration was 162.3 µM in the plasma and 51.8 µM in the aqueous humour. No correlation was observed between these two taurine concentrations, which exhibited a ratio close to 3. Further studies will determine if these taurine concentrations are changed in glaucomatous dogs.


Assuntos
Humor Aquoso/metabolismo , Cães/sangue , Taurina/sangue , Animais , Cruzamento , Cistina/sangue , Dieta , Feminino , Saúde , Masculino , Metionina/sangue , Projetos Piloto , Taurina/biossíntese
14.
Vet Ophthalmol ; 15 Suppl 2: 105-15, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22616780

RESUMO

OBJECTIVE: To obtain images of anterior and posterior segments of the eye using a slit-lamp (SL)/spectral domain (SD) optical coherence tomography (OCT) integrated system designed for the human eye, in the cat, dog, minipig and monkey. ANIMALS STUDIED: One healthy adult monkey, one healthy adult minipig, one healthy adult dog, one healthy adult cat, and three cats and four dogs affected by corneal or retinal diseases. PROCEDURE: A SL SCAN-1 SD-OCT, which is a slit-lamp SL-D7 that contains an integrated OCT module and a fundus viewer, was used to generate OCT images (512-2048), while simultaneously taking 'en-face' slit-lamp images (efSL). OCT images were obtained under sedation or anesthesia. These images were compared to histological retinal sections obtained from a monkey, a minipig, a dog, and a cat. RESULTS: 'en-face' slit-lamp images and OCT images of the ocular tissues were obtained allowing for the identification of different corneal and retinal layers in all animal species. Measurements of the total retinal thickness (TRT) from the inner limiting membrane to the retinal pigment epithelium were performed in various regions throughout the retina. Reduction in TRT was consistent with clinical features of retinal degeneration identified in dogs and cats. CONCLUSION: This noninvasive procedure is useful for both experimental and clinical assessments of ocular tissue damage. Images of anterior and posterior segments are readily obtained under routine clinical conditions. Future studies are warranted to establish normal OCT data in our patients with this new instrument.


Assuntos
Segmento Anterior do Olho/anatomia & histologia , Técnicas de Diagnóstico Oftalmológico/veterinária , Disco Óptico/anatomia & histologia , Segmento Posterior do Olho/anatomia & histologia , Tomografia de Coerência Óptica/veterinária , Animais , Segmento Anterior do Olho/patologia , Técnicas de Diagnóstico Oftalmológico/instrumentação , Oftalmopatias/diagnóstico , Oftalmopatias/patologia , Oftalmopatias/veterinária , Feminino , Masculino , Segmento Posterior do Olho/patologia , Especificidade da Espécie , Tomografia de Coerência Óptica/métodos
15.
Vet Ophthalmol ; 14(6): 365-77, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22050735

RESUMO

PURPOSE: The goal of this study was to report on the advantages and limitations of the pig and feline models for experimental in vivo corneal transplantation. METHODS: Ten healthy domestic pigs and ten healthy cats were used. Full thickness penetrating keratoplasty was performed using autologous (eight cases), allogeneic (seven cases) or human xenogeneic (three cases) tissue. In two other cases, the inflammatory response to partial thickness trephination (without transplantation) was evaluated. Eyes were assessed daily before and after surgery by slit-lamp, pachymetry, and tonometry. A transparency score ranging from 0 (opaque graft) to 4 (clear graft) was used, based on the slit-lamp examination. Optical coherence tomography, histology, and electron microscopy were performed postmortem. RESULTS: In the pig, the mean (±SD) transparency score for the eight full thickness grafts was 0.88 ± 0.99, ranging from 0 to 3. In the feline model, the mean transparency score for the seven uncomplicated grafts was 3.93 ± 0.19, ranging from 3.5 to 4. Both negative controls without endothelium remained opaque at all time. Intraoperative tendency for iris incarceration into the wound, rapid corneal swelling, suture cheese wiring, and postoperative intraocular inflammation were the main factors jeopardizing the functional success of the corneal transplant in the pig model. CONCLUSION: Suboptimal functional results were obtained after full thickness corneal transplantation in the pig model, while in the feline model, the same protocol yielded uneventful surgeries and clear transplants, with functional results similar to those achieved in human subjects.


Assuntos
Doenças do Gato/cirurgia , Transplante de Córnea/veterinária , Modelos Animais de Doenças , Doenças dos Suínos/cirurgia , Animais , Gatos , Córnea/patologia , Córnea/cirurgia , Transplante de Córnea/métodos , Feminino , Sobrevivência de Enxerto , Pressão Intraocular , Ceratoplastia Penetrante/métodos , Ceratoplastia Penetrante/veterinária , Masculino , Complicações Pós-Operatórias/veterinária , Suínos , Tomografia de Coerência Óptica/veterinária
16.
Vet Ophthalmol ; 13(6): 369-76, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21182721

RESUMO

PURPOSE: To perform cellular-level in vivo imaging of the feline retina using an adaptive optics flood illumination fundus camera (AO FIFC) designed for the human eye. MATERIALS AND METHODS: Cellular-level images were obtained from three eyes of two normal sedated cats. Ocular aberrations were corrected using an AO system based on a 52-acuator electromagnetic deformable mirror and a 1024 lenslet Hartmann-Shack sensor (both Imagine Eyes, Orsay, France). A square 3°×3° area of the ocular fundus was flood-illuminated by a pulsed LED emitting at 850 nm and imaged onto a low-noise, high-resolution CCD camera. The animal's pupils were dilated and the effective pupil size was set to 7.5 mm. Conjunctival atraumatic clips were used to avoid eyeball movements and eyelid closure. The cornea was artificially hydrated throughout the experiments. Each acquisition consisted of 20 consecutive images, out of which 10 were numerically averaged to produce an enhanced final image. RESULTS: The total amount of ocular aberrations was greatly reduced by the AO correction, from 2.4 to 0.21 microns root mean square on average. The resulting images presented white dots distributed at a density similar to that of cone photoreceptors and they allowed us to visualize small blood vessels and nerve fiber bundles at a higher resolution than classically obtained with conventional fundus photography. CONCLUSION: Retinal imaging with cellular resolution was feasible in cats under sedation using an AO FIFC designed for human eyes without any optical modification. The AO FIFC technology could find new applications in clinical, pharmacological, and toxicological investigations.


Assuntos
Gatos/anatomia & histologia , Diagnóstico por Imagem/veterinária , Oftalmoscopia/veterinária , Retina/anatomia & histologia , Animais , Diagnóstico por Imagem/instrumentação , Fenômenos Ópticos
17.
Neurobiol Dis ; 38(1): 47-58, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20060471

RESUMO

Several strategies have been proposed to restore useful vision following photoreceptor degeneration. However, a very few studies have investigated late anatomical changes and functional state of residual retinal neurons after complete photoreceptor loss. We investigated the progressive degeneration of retinal ganglion cells (RGCs) in P23H rats. The RGC multielectrode array recordings indicated lower firing rates, disappearance of broad-scale, and maintenance of short-scale pairwise correlations. Up to 11% of RGCs displayed repetitive and often correlated spike discharges, reminiscent of developmental rhythmic activity, which could be reversibly suppressed by blockade of the AMPA/kainite glutamate receptors. RGCs in P23H rats remain sensitive to local electrical stimulation, generating short-latency responses as in the normal retina. These results provide evidence that, despite the demonstrated RGC degeneration, remaining active RGCs maintain their basic physiological and network properties with some emerging functional changes such as the spontaneous rhythmic activity in late stages of the degenerative disease.


Assuntos
Degeneração Neural/patologia , Células Fotorreceptoras de Vertebrados/patologia , Recuperação de Função Fisiológica/genética , Degeneração Retiniana/patologia , Degeneração Retiniana/fisiopatologia , Células Ganglionares da Retina/patologia , Potenciais de Ação/genética , Adaptação Fisiológica/genética , Animais , Modelos Animais de Doenças , Progressão da Doença , Estimulação Elétrica , Eletrorretinografia , Antagonistas de Aminoácidos Excitatórios , Predisposição Genética para Doença , Degeneração Neural/genética , Degeneração Neural/fisiopatologia , Técnicas de Cultura de Órgãos , Periodicidade , Ratos , Ratos Mutantes , Ratos Sprague-Dawley , Receptores de Glutamato/efeitos dos fármacos , Receptores de Glutamato/metabolismo , Degeneração Retiniana/genética , Células Ganglionares da Retina/fisiologia , Transmissão Sináptica/genética , Fatores de Tempo
18.
J Circadian Rhythms ; 7: 14, 2009 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-19922677

RESUMO

BACKGROUND: In the eye, melatonin plays a role in promoting light sensitivity at night and modulating many aspects of circadian retinal physiology. It is also an inhibitor of retinal dopamine, which is a promoter of day vision through the cone system. Consequently, it is possible that oral melatonin (an inhibitor of retinal dopamine) taken to alleviate circadian disorders may affect cone functioning. Our aim was to assess the impact of melatonin on the cone response of the human retina using electroretinography (ERG). METHODS: Twelve healthy participants aged between 18 to 52 years old were submitted to a placebo-controlled, double-blind, crossover, and counterbalanced-order design. The subjects were tested on 2 sessions beginning first with a baseline ERG, followed by the administration of the placebo or melatonin condition and then, 30 min later, a second ERG to test the effect. RESULTS: Following oral melatonin administration, a significant decrease of about 8% of the cone maximal response was observed (mean 6.9 muV +/- SEM 2.0; P = 0.0065) along with a prolonged b-wave implicit time of 0.4 ms +/- 0.1, 50 minutes after ingestion. CONCLUSION: Oral melatonin appears to reach the eye through the circulation. When it is administered at a time of day when it is not usually present, melatonin appears to reduce input to retinal cones. We believe that the impact of melatonin on retinal function should be taken into consideration when used without supervision in chronic self-medication for sleep or circadian disorder treatment.

19.
Graefes Arch Clin Exp Ophthalmol ; 246(11): 1505-17, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18709385

RESUMO

BACKGROUND: The development of a functional retinal prosthesis for acquired blindness is a great challenge. Rapid progress in the field over the last 15 years would not have been possible without extensive animal experimentation pertaining to device design and fabrication, biocompatibility, stimulation parameters and functional responses. This paper presents an overview of in vivo animal research related to retinal prosthetics, and aims to summarize the relevant studies. METHODS: A Pubmed search of the English language literature was performed. The key search terms were: retinal implant, retinal prosthesis, artificial vision, rat, rabbit, cat, dog, sheep, pig, minipig. In addition a manual search was performed based on references quoted in the articles retrieved through Pubmed. RESULTS: We identified 50 articles relevant to in vivo animal experimentation directly related to the development of a retinal implant. The highest number of publications related to the cat (n = 18). CONCLUSION: The contribution of animal models to the development of retinal prosthetic devices has been enormous, and has led to human feasibility studies. Grey areas remain regarding long-term tissue-implant interactions, biomaterials, prosthesis design and neural adaptation. Animals will continue to play a key role in this rapidly evolving field.


Assuntos
Pesquisa Biomédica , Cegueira/cirurgia , Modelos Animais , Próteses e Implantes , Implantação de Prótese , Retina/cirurgia , Animais
20.
Invest Ophthalmol Vis Sci ; 49(11): 5168-74, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18539931

RESUMO

PURPOSE: The authors recently used topical endoscopy to image the mouse eye fundus. Here, they widened the field of application for this ophthalmologic tool, imaging both the posterior and the anterior eye segments in larger animals commonly encountered in research laboratories and veterinary clinics. METHODS: Pupils were dilated, and local anesthetic and gel were applied to the animal cornea. The endoscopic probe was placed in contact with the cornea of conscious rats, sedated cats and dogs, anesthetized sheep, and nonhuman primates. RESULTS: High-resolution digital images of the eye fundus were obtained in all investigated animals using the endoscopic probe along the eye axis. Arteriovenous filling time was monitored with fluorescein angiography in pigmented rats. The retinal periphery and ciliary bodies could be visualized with the probe placed at an oblique angle. The probe was inclined further to observe the iridocorneal angle such that the pectinate ligaments could be seen at high resolution in cats. The authors used the probe on eyes with retinal detachment, luxation of a cataractous lens, and pigment infiltration in the iridocorneal angle, demonstrating its potential use in eye diseases. CONCLUSIONS: This topical endoscopic technique provides a unique tool for single eye examinations. The authors obtained a circular view of the anterior (iridocorneal angle) and the posterior (fundus) eye segments from all animal species studied. This technique is inexpensive and easy to use. It can be easily moved to the eye of the patient who cannot move to stand in front of classic apparatus, offering new opportunities in ophthalmology.


Assuntos
Corpo Ciliar/patologia , Córnea/patologia , Técnicas de Diagnóstico Oftalmológico/economia , Endoscopia/economia , Oftalmopatias/diagnóstico , Iris/patologia , Retina/patologia , Animais , Callithrix , Gatos , Análise Custo-Benefício , Técnicas de Diagnóstico Oftalmológico/instrumentação , Modelos Animais de Doenças , Cães , Endoscópios/economia , Endoscopia/métodos , Desenho de Equipamento , Haplorrinos , Camundongos , Ratos , Reprodutibilidade dos Testes , Ovinos
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