6 research outputs found
SubFoveal Choroidal Imaging in High Myopic Nepalese Cohort
Current image captioning models produce fluent captions, but they rely on a one-size-fits-all approach that does not take into account the preferences of individual end-users. We present a method to generate descriptions with an adjustable amount of content that can be set at inference-time, thus providing a step toward a more user centered approach to image captioning
Immunotoxin-Induced Ablation of the Intrinsically Photosensitive Retinal Ganglion Cells in Rhesus Monkeys
Purpose: Intrinsically photosensitive retinal ganglion cells (ipRGCs) contain the photopigment melanopsin, and are primarily involved in non-image forming functions, such as the pupillary light reflex and circadian rhythm entrainment. The goal of this study was to develop and validate a targeted ipRGC immunotoxin to ultimately examine the role of ipRGCs in macaque monkeys.Methods: An immunotoxin for the macaque melanopsin gene (OPN4), consisting of a saporin-conjugated antibody directed at the N-terminus, was prepared in solutions of 0.316, 1, 3.16, 10, and 50 μg in vehicle, and delivered intravitreally to the right eye of six rhesus monkeys, respectively. Left eyes were injected with vehicle only. The pupillary light reflex (PLR), the ipRGC-driven post illumination pupil response (PIPR), and electroretinograms (ERGs) were recorded before and after injection. For pupil measurements, 1 and 5 s pulses of light were presented to the dilated right eye while the left pupil was imaged. Stimulation included 651 nm (133 cd/m2), and 4 intensities of 456 nm (16–500 cd/m2) light. Maximum pupil constriction and the 6 s PIPR were calculated. Retinal imaging was performed with optical coherence tomography (OCT), and eyes underwent OPN4 immunohistochemistry to evaluate immunotoxin specificity and ipRGC loss.Results: Before injection, animals showed robust pupil responses to 1 and 5 s blue light. After injection, baseline pupil size increased 12 ± 17%, maximum pupil constriction decreased, and the PIPR, a marker of ipRGC activity, was eliminated in all but the lowest immunotoxin concentration. For the highest concentrations, some inflammation and structural changes were observed with OCT, while eyes injected with lower concentrations appeared normal. ERG responses showed better preserved retinal function with lower concentrations. Immunohistochemistry showed 80–100% ipRGC elimination with the higher doses being more effective; however this could be partly due to inflammation that occurred at the higher concentrations.Conclusion: Findings demonstrated that the OPN4 macaque immunotoxin was specific for ipRGCs, and induced a graded reduction in the PLR, as well as, in ipRGC-driven pupil response with concentration. Further investigation of the effects of ipRGC ablation on ocular and systemic circadian rhythms and the pupil in rhesus monkeys will provide a better understanding of the role of ipRGCs in primates
Visual Function and Retinal Structure with Ganglion Cell Ablation and in Myopia
Purpose: The guinea pig is a model of human retinal physiology and pathology. However, detailed understanding of retinal structure and function is lacking. Here we describe retinal structure and function in healthy guinea pigs, and develop a model of ganglion cell loss. Using imaging analysis techniques developed in these studies, we then evaluated ocular parameters in school age children as a function of age, axial length, and refraction.
Methods: 1) In guinea pigs, spatial frequency discrimination was evaluated using optomotor responses. Retinal function was assessed using flash and pattern electroretinogram (ERG). Structure was assessed in vivo using spectral domain optical coherence tomography (SD-OCT. Retrograde retinal ganglion cell degeneration was induced with unilateral optic nerve crush, and changes in retinal structure and visual function were examined. Retinal ganglion cell density and distribution were quantified histologically. 2) In school age children (n = 53), the optic nerve head, lamina cribrosa, retina, and choroid were evaluated using SD-OCT. Images were analyzed in MATLAB and assessed in relation to age, axial length, and refractive error.
Results: 1) Mean spatial frequency discrimination of guinea pigs was 1.65 cycles/degree. The photopic negative response (PhNR) and the oscillatory potentials (OPs) were similar to those in primates. The visual streak was localized the superior retina, with peak ganglion cell density of 1621±129 cells/mm2. With unilateral optic nerve crush, loss of optomotor responses, thinning of retinal nerve fiber layer, and reduction of PhNR and OP1 amplitudes were observed. Pattern ERG responses were largely unaffected. 2) In children, minimum foveal thickness and retinal thickness increased with age. Bruch’s membrane opening area increased with myopic refractive error, and vertical cup-to-disc ratio decreased with increasing axial length and myopic refractive error.
Conclusion: We demonstrated that retinal ganglion cells contribute to the PhNR and OPs of flash ERG in guinea pigs. These findings will be valuable when assessing progression of ocular disease in this animal model. In school age children, we described normative values for retinal and optic nerve head parameters, and demonstrate that ocular remodeling occurs in school age children with normal eye growth and during early stages of myopia.Optometry, College o
In Vivo Imaging of the Retina, Choroid, and Optic Nerve Head in Guinea Pigs
<p><i>Purpose:</i> Guinea pigs are increasingly being used as a model of myopia, and may also represent a novel model of glaucoma. Here, optical coherence tomography (OCT) imaging was performed in guinea pigs. <i>In vivo</i> measurements of retinal, choroidal, and optic nerve head parameters were compared with histology, and repeatability and interocular variations were assessed.</p> <p><i>Methods:</i> OCT imaging and histology were performed on adult guinea pigs (<i>n</i> = 9). Using a custom program in MATLAB, total retina, ganglion cell/nerve fiber layer (GC/NFL), outer retina, and choroid thicknesses were determined. Additionally, Bruch’s membrane opening (BMO) area and diameter, and minimum rim width were calculated. Intraobserver, interocular, and intersession coefficients of variation (CV) and intraclass correlation coefficients (ICC) were assessed.</p> <p><i>Results:</i> Retina, GC/NFL, outer retina and choroid thicknesses from <i>in vivo</i> OCT imaging were 147.7 ± 5.8 μm, 59.2 ± 4.5 μm, 72.4 ± 2.4 μm, and 64.8 ± 11.6 μm, respectively. Interocular CV ranged from 1.8% to 11% (paired <i>t</i>-test, <i>p</i> = 0.16 to 0.81), and intersession CV ranged from 1.1% to 5.6% (<i>p</i> = 0.12 to 0.82), with the choroid showing the greatest variability. BMO area was 0.192 ± 0.023 mm<sup>2</sup>, and diameter was 493.79 ± 31.89 μm, with intersession CV of 3.3% and 1.7%, respectively. Hyper reflective retinal layers in OCT correlated with plexiform and RPE layers in histology.</p> <p><i>Conclusion:</i><i>In vivo</i> OCT imaging and quantification of guinea pig retina and optic nerve head parameters were repeatable and similar between eyes of the same animal. <i>In vivo</i> visibility of retinal cell layers correlated well with histological images.</p> <p><b>Abbreviations:</b> optic nerve head (ONH), retinal ganglion cell (RGC), spectral domain optical coherence tomography (SD-OCT), enhanced depth imaging (EDI), minimum rim width (MRW), hematoxylin and eosin (H & E)</p