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Photoreceptor degeneration in a new Cacna1f mutant mouse model
摘要： The Cacna1f gene encodes the α1F subunit of an L-type voltage-gated calcium channel, Cav1.4. In photoreceptor synaptic terminals, Cav1.4 channels mediate glutamate release and postsynaptic responses associated with visual signal transmission. We have discovered a new Cacna1f mutation in nob9 mice, which display more severe phenotypes than do nob2 mice. To characterize the nob9 phenotype at different ages, we examined the murine fundus, applied retinal optical coherence tomography, measured flash electroretinograms (ERGs) in vivo, and analyzed the retinal histology in vitro. After identifying the X-linked recessive inheritance trait, we sequenced Cacna1f as the candidate gene. Mutations in this gene were detected by polymerase chain reaction (PCR) and confirmed by restriction fragment length polymorphism. Morphologically, an early-onset of retinal disorder was detected, and the degeneration of the outer plexiform layers progressed rapidly. Moreover, the mutant mice showed drastically reduced scotopic ERGs with increasing age. In 14-month-old nob9 retinas, immunostaining of cone opsins demonstrated a reduction in the number of short-wavelength opsins (S-opsins) to 54% of wild-type levels, and almost no middle-wavelength opsins (M-opsins) were observed. No cone ERGs could be detected from residual cones, in which S-opsins abnormally migrated to inner segments of the photoreceptors. The mutations of the Cacna1f gene in nob9 mice involved both a single nucleotide G to A transition and a 10-nucleotide insertion, the latter resulting in a frame-shift mutation in exon 14.
关键词： X-linked recessive inheritance,Electroretinogram,Congenital stationary night blindness,Mice,Cone opsins
更新于2025-09-10 09:29:36
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Asymptomatic Unexplained Visual Field Loss Diagnosed as Early Retinitis Pigmentosa without Pigmentation: A Case Report
摘要： Purpose: We report a case of asymptomatic unexplained visual field loss diagnosed as early retinitis pigmentosa (RP) without pigmentation. Case summary: A 33-year-old woman was referred to us with a constricted visual field (C24-2) before laser-assisted in-situ keratomileusis surgery. The visual field test (C30-2) revealed significantly decreased sensitivity between 15 to 25 degrees in both eyes. Close fundus examination revealed a subtle greyish retinal atrophic lesion along the vascular arcade and fluorescein angiography revealed a window defect in accordance with a retinal atrophic lesion in both eyes. Optical coherence tomography showed decreased retinal thickness around the macula. Electroretinogram revealed decreased b waves in rod response. Based on these findings, we diagnosed the patient with early RP without pigmentation. Conclusions: The possibility of early RP without pigmentation presenting as slight atrophy around the macula without significant pigmental degeneration should also be considered if a patient presents with peripheral visual field constriction without other symptoms. The ophthalmologist should ensure that the location of the visual field defect matches the location of the lesion. In addition, a detailed fundus examination with macular optical coherence tomography can be helpful to diagnose such a lesion.
关键词： Constricted central visual field,Electroretinogram,Macular optical coherence tomography,Early retinitis pigmentosa (RP) without pigmentation
更新于2025-09-09 09:28:46
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Remote Ischemia Influences the Responsiveness of the Retina: Observations in the Rat
摘要： Remote ischemic preconditioning (RIP) has been found to be protective of heart and brain against ischemic injury. We have tested the effects of RIP on retinal function using the electroretinogram. METHODS. Ischemia remote from the retina was induced in one hindlimb, using a pressure cuff applied for between 5 and 10 minutes. A temperature probe on the footpad con?rmed blockage of the circulation. To test the impact of RIP on retinal function, we recorded the dark-adapted ?ash electroretinogram (ERG) in four groups (n ? 5 per group) of Sprague-Dawley rats (sham, 5-minute, 10-minute, and 2 3 5-minute ischemia). Heart rate, breath rate, and peripheral oxygen saturation were monitored using infrared pulse oximetry. RESULTS. RIP increased both the a- and b-waves by up to 14%, more markedly after the longer periods (10 minutes or 2 3 5 minutes) of ischemia. The effect was tested up to 30 minutes after ischemia and retested at 1 week and 1 month. RIP did not appear to accelerate the initial stages of recovery from photopigment bleach. Systemic oxygen saturation, heart rate, and respiration did not vary consistently during or after remote ischemia. CONCLUSIONS. The effect of RIP on the ERG is a novel ?nding. Possible mechanisms of this effect are discussed and related to the idea of neuroprotection and to fundamentals of the electroretinogram.
关键词： remote ischemic preconditioning,ATP-sensitive potassium channel,dark adaptation,adenosine,electroretinogram,retina
更新于2025-09-09 09:28:46
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Connexin43 Mimetic Peptide Improves Retinal Function and Reduces Inflammation in a Light-Damaged Albino Rat Model
摘要： PURPOSE. Drugs that regulate connexin43 (Cx43) gap junction channels can reduce the spread of injury and improve functional outcomes after nervous system trauma. In the eye, Cx43 expression increases in the choroid following light damage. The aim of this study was to investigate whether Cx43 hemichannel block could preserve retinal function postinjury. METHODS. Light damage was induced by exposure of adult albino Sprague-Dawley rats to 2700 Lux light for 24 hours. Intravitreal injections of a Cx43 mimetic peptide hemichannel blocker, Peptide5, or sham were administered 2 hours after the onset and at the end of the light damage period. Retinal function was assessed by electroretinogram and inflammatory responses in the choroid and retina were assessed using immunohistochemistry (ionized calcium binding adaptor molecule 1 [Iba-1], leukocyte common antigen [CD45], glial fibrillary acidic protein [GFAP]). RESULTS. Light-damaged rat eyes had (1) reduced neuronal responses in both the rod and cone pathways and (2) marked inflammatory responses in the choroid and retina. Peptide5 significantly preserved function of photoreceptoral and postphotoreceptoral neurons in these animals. This was evident 24 hours after injury and 2 weeks later, as shown by improved mixed a-wave and mixed b-wave amplitudes, isolated rod PII and PIII amplitudes, and cone PII responses when compared with sham-treated controls. Retinal thinning and inflammation were also significantly reduced in Peptide5-treated eyes when compared with sham-treated controls. CONCLUSIONS. Blocking Cx43 hemichannels after light damage can significantly improve functional outcomes of neurons in both the rod and cone photo-transduction pathways in the light-damaged animal model, likely by reducing choroid inflammation and suppressing the glial-mediated inflammatory response. These data may have relevance for the treatment of conditions such as diabetic retinopathy and age-related macular degeneration.
关键词： retina,choroid,light damage,inflammation,connexin43,electroretinogram
更新于2025-09-09 09:28:46
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Next Generation PERG Method: Expanding the Response Dynamic Range and Capturing Response Adaptation
摘要： Purpose: To compare a new method for steady-state pattern electroretinogram (PERGx) with a validated method (PERGLA) in normal controls and in patients with optic neuropathy. Methods: PERGx and PERGLA were recorded in a mixed population (n ? 33, 66 eyes) of younger controls (C1; n ? 10, age 38 6 8.3 years), older controls (C2; n ? 11, 57.9 6 8.09 years), patients with early manifest glaucoma (G; n ? 7, 65.7 611.6 years), and patients with nonarteritic ischemic optic neuropathy (N; n ? 5, mean age 59.4 6 8.6 years). The PERGx stimulus was a black-white horizontal grating generated on a 14 3 14 cm LED display (1.6 cycles/deg, 15.63 reversals/s, 98% contrast, 800 cd/m2 mean luminance, 258 field). PERGx signal and noise were averaged over 1024 epochs (~2 minutes) and Fourier analyzed to retrieve amplitude and phase. Partial averages (16 successive samples of 64 epochs each) were also analyzed to quantify progressive changes over recording time (adaptation). Results: PERGLA and PERGx amplitudes and latencies were correlated (Amplitude R2 ? 0.59, Latency R2 ? 0.39, both P , 0.0001) and were similarly altered in disease. Compared to PERGLA, however, PERGx had shorter (16 ms) latency, higher (1.393) lower (0.373) noise, and higher (4.23) signal-to-noise ratio. PERGx amplitude, displayed marked amplitude adaptation in C1 and C2 groups and no significant adaptation in G and N groups. Conclusions: The PERGx high signal-to-noise ratio may allow meaningful recording in advanced stages of optic nerve disorders. it quantifies response adaptation, which may be selectively altered in glaucoma and optic neuropathy.
关键词： signal-to-noise ratio,non-arteritic ischemic optic neuropathy,neural adaptation,glaucoma,pattern electroretinogram
更新于2025-09-04 15:30:14
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The Effect of PKCα on the Light Response of Rod Bipolar Cells in the Mouse Retina
摘要： PURPOSE. Protein kinase C a (PKCa) is abundantly expressed in rod bipolar cells (RBCs) in the retina, yet the physiological function of PKCa in these cells is not well understood. To elucidate the role of PKCa in visual processing in the eye, we examined the effect of genetic deletion of PKCa on the ERG and on RBC light responses in the mouse. METHODS. Immuno?uorescent labeling was performed on wild-type (WT), TRPM1 knockout, and PKCa knockout (PKC-KO) retina. Scotopic and photopic ERGs were recorded from WT and PKC-KO mice. Light responses of RBCs were measured using whole-cell recordings in retinal slices from WT and PKC-KO mice. RESULTS. Protein kinase C alpha expression in RBCs is correlated with the activity state of the cell. Rod bipolar cells dendrites are a major site of PKCa phosphorylation. Electroretinogram recordings indicated that loss of PKCa affects the scotopic b-wave, including a larger peak amplitude, longer implicit time, and broader width of the b-wave. There were no differences in the ERG a- or c-wave between PKCa KO and WT mice, indicating no measurable effect of PKCa in photoreceptors or the RPE. The photopic ERG was unaffected consistent with the lack of detectable PKCa in cone bipolar cells. Whole-cell recordings from RBCs in PKC-KO retinal slices revealed that, compared with WT, RBC light responses in the PKC-KO retina are delayed and of longer duration. CONCLUSIONS. Protein kinase C alpha plays an important modulatory role in RBCs, regulating both the peak amplitude and temporal properties of the RBC light response in the rod visual pathway.
关键词： electroretinogram,protein kinase C,b-wave,rod bipolar cell
更新于2025-09-04 15:30:14