Electron Beam-Irradiated g-C<sub>3</sub>N<sub>4</sub>/Ti<sub>3</sub>C<sub>2</sub> Nanocomposite Embedded in PVA/SA Hydrogel: An Integrated Platform with Enhanced Photocatalytic Antibacterial Activity
Rui Feng, Xuguang Chen, Yue Wu
et al.
Photodynamic antibacterial therapy presents a promising strategy for combating bacterial infections due to its non-invasive nature and low potential for inducing resistance. In this work, we developed a series of electron beam-modified graphitic carbon nitride (g-C<sub>3</sub>N<sub>4</sub>, CN) and titanium carbide (Ti<sub>3</sub>C<sub>2</sub>, TC) nanocomposites, which were subsequently incorporated into polyvinyl alcohol/sodium alginate (PVA/SA) hydrogels through physical cross-linking. The optimized 200CN/1TC composite hydrogel (where 200CN denotes 200 kGy irradiation dose, and 1TC represents 1 wt% TC content) maintained excellent biocompatibility with cell viability exceeding 80% even at the highest nanomaterial loading (8% 200CN/1TC). Notably, the 8% 200CN/1TC composite hydrogel displayed substantial antibacterial activity, forming inhibition zones of 12.3 mm and 10.8 mm against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>, respectively. The improved performance may be explained by the combined effects of enhanced electron transfer between the component materials and the unique two-dimensional structure of the nanocomposites, though further investigation is required to fully elucidate the underlying mechanisms. This study provides a feasible approach for developing efficient antibacterial hydrogel systems and offers valuable perspectives on the design of nanomaterial-based biomedical materials for wound healing and infection control applications.
A rare case of uniocular central retinal artery occlusion post laminotomy with lumbar decompression surgery
Sneha Punjabi, Divya Vaidya, Harsha Pagad
et al.
Presenting a rare case of Unilateral Central Retinal Artery Occlusion (CRAO) following spinal surgery. CRAO following spinal surgery is a rare complication. Central retinal arterial occlusion (CRAO) is an ophthalmic emergency characterized by the sudden blockage of the central retinal artery, the primary blood vessel supplying the retina. This blockage leads to rapid, painless, severe vision loss in the affected eye. One of the leading causes of CRAO is an embolus that obstructs the artery, from the carotid artery or the heart. The blood flow interruption to the retina results in ischemia, causing damage to retinal cells. Unfortunately, the prognosis for visual recovery in CRAO is limited, making early diagnosis critical in managing this serious eye condition.
Influence of drainage retinotomy on anatomical and visual outcomes of pars plana vitrectomy for primary rhegmatogenous retinal detachment
, Andrew Davies, Imran Khan
et al.
Objectives To assess the influence of drainage retinotomy (DrR) on anatomical and visual outcomes of pars plana vitrectomy (PPV) for primary uncomplicated rhegmatogenous retinal detachment (RD), compared with drainage through pre-existing retinal break (PRB).Methods and analysis Retrospective study on patients treated with PPV for RD. Prospectively collected data were extracted from the Britain & Eire Association of Vitreoretinal Surgeons and European Society of Retina Specialists (EURETINA) RD database, including baseline features, surgical details, and anatomical and functional outcomes. Inclusion criteria were as follows: uncomplicated PPV, gas tamponade, drainage through DrR or PRB, surgeons with >100 cases recorded. Exclusion criteria were as follows: age <16, <2-month follow-up, ocular comorbidity, proliferative vitreoretinopathy ≥grade C, giant retinal tear, tamponade other than gas. Full propensity score matching resulted in matched groups to mitigate confounding bias. Subsequent multivariable linear regression was performed for postoperative best-corrected visual acuity (BCVA) as dependent variable, and Firth penalised logistic regression with DrR, single-surgery anatomical success (SSAS), epiretinal membrane (ERM) and macular fold as dependent dichotomised variables on matched data.Results Of 12 504 eyes extracted, 4175 were included. Of these, 3432 (82.2%) had PRB drainage (non-DrR group) and 743 (17.8%) a DrR (DrR group). Final median (IQR) BCVA was 0.18 (0.14–0.48) in the non-DrR group and 0.20 (0.18–0.48) in the DrR group (p=0.072). SSAS rate was 93.4% and 91% (OR 0.71 (95% CI 0.54 to 0.95)) and postoperative ERM rate 1.6% and 4.2% (OR 2.63 (95% CI 1.68 to 4.10)) in the non-DrR and DrR groups, respectively. On multivariable regression, DrR was associated with postoperative ERM (p=0.011), but not with final BCVA, SSAS and macular folds (p=0.633, 0.149 and 0.085, respectively).Conclusion Our study confirmed the association between DrR and increased risk of developing ERM; however, DrR does not appear to impact significantly on other outcomes.
Endophthalmitis after intravitreal injection with or without triamcinolone – A 10-year investigation in a tertiary hospital
Yen-Ju Chen, Cyuan-Yi Yeh, Cheng-Kuo Cheng
PURPOSE:
Intravitreal injections (IVIs) have been the most important treatment strategies in retinal diseases. With the increasing use of IVIs, the incidence of endophthalmitis has inevitably risen. Triamcinolone acetonide (TA) used in IVIs has been suspected as a risk factor for post-IVI endophthalmitis. This study investigates the incidence, clinical presentations, and microscopic findings of post-IVI endophthalmitis with or without TA, aiming to provide a better understanding of this issue.
MATERIALS AND METHODS:
This retrospective study included patients receiving IVIs at a tertiary referral center from September 2010 to August 2020. Injections were performed under sterile conditions, and endophthalmitis was diagnosed based on acute ocular symptoms within 6 weeks postinjection. Statistical analysis was preformed between endophthalmitis with or without TA.
RESULTS:
Out of 18,365 IVIs, the incidence of endophthalmitis was 0.038%. The incidence of TA-associated endophthalmitis (TAAE) (5 in 939 IVIs, 0.532%) was significantly higher (P < 0.0001) than that of non-TAAE (2 in 17,426 IVIs, 0.011%). All five TAAE cases were culture negative, while the two non-TAAE cases were culture positive with Staphylococcus epidermidis (P < 0.0001). The outcomes for TAAE were generally good, with patients returning to their preendophthalmitis vision levels. Risk factors for TAAE included prior IVIs and prior TA injections. Microscopy revealed fern-like crystalline materials in the anterior chamber of one TAAE case.
CONCLUSION:
This study highlights that TA is significantly associated with a higher incidence of post-IVI endophthalmitis, which is also significantly associated with culture-negative results. This implies the possibility of a noninfectious cause in TAAE.
Preliminary findings from a retrospective comparative study on a novel hydrophobic C-loop monofocal intraocular lens
Youngsub Eom, Jeongmin Kim, Hungwon Tchah
et al.
Abstract To investigate visual outcomes and optical performance of a new non-constant aberration aspheric monofocal intraocular lens (IOL). This study included consecutive patients who underwent phacoemulsification with implantation of either the CT LUCIA® 621P intraocular lens (Carl Zeiss Meditec AG, Jena, Germany; 32 eyes, 25 patients) or the Tecnis® ZCB00 intraocular lens (Johnson & Johnson Vision, Santa Ana, CA, USA; 38 eyes, 27 patients). Monocular uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), uncorrected intermediate visual acuity (UIVA), and objective optical quality were measured 3 months after surgery. The optical bench test measured the root mean square of the modulation transfer function (MTTRMS) of each IOL at defocus levels between +1.00 D and −2.50 D at intervals of 0.25 D at varying pupil sizes (2.0–5.0 mm) in 1.0 mm steps. There was no difference in UDVA, UNVA, and objective optical quality between CT LUCIA and ZCB00 groups. On the other hand, UIVA was higher in the CT LUCIA group (0.19 ± 0.12 logMAR) compared to the ZCB00 group (0.32 ± 0.05 logMAR; p < 0.001). For all tested pupil sizes, the MTFRMS values for both CT LUCIA and ZCB00 IOLs were similar across defocus ranges from +1.00 to −0.75 D. However, the CT LUCIA IOL consistently exhibited higher MTFRMS values than the ZCB00 IOL at defocus levels from −1.25 to − 2.50 D. The CT LUCIA IOL provides comparable distance visual acuity and optical quality to ZCB00 IOL, with superior performance at intermediate distances.
Comments on: Visual outcomes following cataract surgery with intraocular lens implantation in vitrectomized eyes among children
Sangeeta Thakur, Nidhi Pandey
Micropulse diode laser therapy in refractory glaucoma
Moctar Issiaka, Khalil Zrikem, Adil Mchachi
et al.
Purpose: Description of safety and efficacy of micropulse Transscleral cyclophotocoagulation as a treatment option for refractory glaucoma. Methods: This is a prospective study including 39 eyes of 31 patients followed for refractory glaucoma, who benefited from transscleral cyclophotocoagulation using a microplused laser. The main indication for the procedure was increased ocular pressure refractory to quadritherapy in various types of glaucoma. The patients were treated using iridex Cyclo G6 laser with a Micropulse P3 infrared probe with a wavelength of 810 nm. The parameters for the procedure were a duration of 90 s per hemisphere with a power of 2000 mW and an energy of 180 J. Both the upper and lower hemispheres were treated in the same procedure, sparing the 3 o'clock and 9 o'clock meridians, and all the patients benefited from a single treatment session. The following parameters were evaluated: ocular pain and overall tolerance; visual acuity; and the evolution of IOP postoperatively up to 9 months. Results: The glaucoma subtypes treated are as follows: primary open-angle glaucoma (n = 05), chronic angle-closure glaucoma (n = 13), neovascular glaucoma (n = 07), aphakic glaucoma (n = 06), malignant glaucoma (n = 04), post-traumatic angle recession (n = 02), and inflammatory glaucoma (n = 02). The mean pre-operative intraocular pressure was 42.3 ± 5.2 mmHg and the mean post-operative intraocular pressure at 9 months was 16.9 ± 1.9 mmHg. The reduction in IOP was 49.9%. The average number of intraocular pressure-lowering medications used prior to surgery was four, and the average number of medications used at the 9-month post-operative visit was 2.0 ± 1.2 (70.3% of patients were on dual therapy). The overall success rate was 60.5%. Conclusions: Micropulse transscleral cyclophotocoagulation appears to be a safe and efficient treatment for refractory glaucoma. Its indications should therefore be broadened and proposed early in various situations.
Eye damage in COVID-19. Part 2: posterior segment complications, neuro-ophthalmic manifestations, vaccination and risk factors
N. I. Kurysheva, O. A. Evdokimova, A. D. Nikitina
Posterior eye segment involvement in COVID-19 has varied manifestations: vascular, inflammatory, and neuronal. All of them are triggered by SARS-CoV-2 virus but they cannot be viewed as exclusively specific to COVID-19. According to the literature, the mean age of the patients varies from 17 to 75 with the median of 50 years. The median duration between the appearance of ophthalmic symptoms and the detection of COVID-19 was 12 days. The disease affects both men and women equally. Direct exposure to the virus, immune-mediated tissue damage, activation of the coagulation system, the prothrombotic state caused by a viral infection, concomitant diseases and medications used in the treatment contribute to the development of eye pathologies. Ophthalmologists should be aware of the possible relations of posterior eye segment pathologies, orbit and neuro-ophthalmic disorders with SARS-CoV-2, as well as the possible exacerbation of chronic forms of inflammatory eye diseases and autoimmune disorders due to anti-COVID-19 vaccination.
Vascular reconstruction of the decellularized biomatrix for whole-organ engineering—a critical perspective and future strategies
Santosh Gupta, Santosh Gupta, Akriti Sharma
et al.
Whole-organ re-engineering is the most challenging goal yet to be achieved in tissue engineering and regenerative medicine. One essential factor in any transplantable and functional tissue engineering is fabricating a perfusable vascular network with macro- and micro-sized blood vessels. Whole-organ development has become more practical with the use of the decellularized organ biomatrix (DOB) as it provides a native biochemical and structural framework for a particular organ. However, reconstructing vasculature and re-endothelialization in the DOB is a highly challenging task and has not been achieved for constructing a clinically transplantable vascularized organ with an efficient perfusable capability. Here, we critically and articulately emphasized factors that have been studied for the vascular reconstruction in the DOB. Furthermore, we highlighted the factors used for vasculature development studies in general and their application in whole-organ vascular reconstruction. We also analyzed in detail the strategies explored so far for vascular reconstruction and angiogenesis in the DOB for functional and perfusable vasculature development. Finally, we discussed some of the crucial factors that have been largely ignored in the vascular reconstruction of the DOB and the future directions that should be addressed systematically.
Case report of the evidence of a spontaneous Reverse Pulfrich effect in monovision after cataract surgery
Victor Rodriguez-Lopez, Carlos Dorronsoro
Abstract Background Cataracts affect the optics of the eye in terms of absorption, blur, and scattering. When cataracts are unilateral, they cause differences between the eyes that can produce visual discomfort and harm binocular vision. These interocular differences can also induce differences in the processing speed of the eyes that may cause a spontaneous Pulfrich effect, a visual illusion provoking important depth misperceptions. Interocular differences in light level, like those present in unilateral cataracts, can cause the Classic Pulfrich effect, and interocular differences in blur, like those present in monovision, a common correction for presbyopia, can cause the Reverse Pulfrich effect. The visual system may be able to adapt, or not, to the new optical condition, depending on the degree of the cataract and the magnitude of the monovision correction. Case presentation Here, we report a unique case of a 45-year-old patient that underwent unilateral cataract surgery resulting in a monovision correction of 2.5 diopters (D): left eye emmetropic after the surgery compensated with a monofocal intraocular lens and right eye myopic with a spherical equivalent of -2.50 D. This patient suffered severe symptoms in binocular vision, which can be explained by a spontaneous Pulfrich effect (a delay measured of 4.82 ms, that could be eliminated with a 0.19 optical density filter). After removing the monovision with clear lens extraction in the second eye, symptoms disappeared. We demonstrate that, at least in this patient, both Classic and Reverse Pulfrich effects coexist after unilateral cataract surgery and that can be readapted by reverting the interocular differences. Besides, we report that the adaptation/readaptation process to the Reverse Pulfrich effect happens in a timeframe of weeks, as opposed to the Classic Pulfrich effect, known to have timeframes of days. Additionally, we used the illusion measured in the laboratory to quantify the relevance of the spontaneous Pulfrich effect in different visual scenarios and tasks, using geometrical models and optic flow algorithms. Conclusions Measuring the different versions of the Pulfrich effect might help to understand the visual discomfort reported by many patients after cataract surgery or with monovision and could guide compensation or intervention strategies.
Whitecoat Adherence in Patients With Primary Open-Angle Glaucoma
Shervonne Poleon, Nouran Sabbagh, Lyne Racette
PurposeWhitecoat adherence refers to improved medication adherence in the days surrounding clinic visits. This may lead to clinical measures that are not representative of those outside of clinical encounters. In glaucoma, whitecoat adherence to prescribed hypotensive therapy may lead to intraocular pressure readings within the target range, which may impact clinical decision-making. We aimed to quantify and identify factors associated with whitecoat adherence.MethodsIn this cohort study, patients with primary open-angle glaucoma were selected from an ongoing longitudinal NIH-funded study if they used hypotensive eyedrops, had a clinic visit during the parent study, and had adherence data during the 28 days evenly bracketing the clinic visit. Adherence within the implementation phase was measured using Medication Event Monitoring System (MEMS) caps. Wilcoxon tests were used to compare mean adherence between the following periods: Pre14−4 (days 14 to 4 preceding the clinic visit) and Pre3−1 (days 3 to 1 preceding the visit); Post1−3 (days 1 to 3 following the clinic visit) and Post4−14 (days 4 to 14 following the visit). Analyses were performed in the full sample and in patients with optimal (≥80%, n = 49) and suboptimal adherence (<80%, n = 17).ResultsSixty-six patients were included, of which 51.5% were female. Mean age was 70.8 ± 8.1 years. In the 6 months evenly bracketing the clinic visit, mean and median adherence were 86.3% (standard deviation = 17.7) and 95.6% (interquartile range = 21.2), respectively. Overall, mean adherence increased from Pre14−4 to Pre3−1 (85.5% ± 21.2 to 88.5% ± 23.2, p = 0.01) and decreased from Post1−3 to Post4−14 (87.0 ± 23.9 to 84.9 ± 23.3, p = 0.02). In patients with optimal adherence, adherence increased from Pre14−4 to Pre3−1 (94.0 ± 11.7 to 97.7 ± 7.4, p = 0.001) and from Post1−3 to Post4−14 (95.2 ± 12.0 to 95.4 ± 5.7, p = 0.007). Whitecoat adherence was not observed in patients with suboptimal adherence.ConclusionWe documented the presence of whitecoat adherence in this cohort. Due to its potential impact on clinical outcomes and decisions, providers should remain vigilant for this phenomenon and prioritize it during patient-provider discussions.
Establishment of a human induced pluripotent stem cell line (CSUASOi008-A) from a type 2 diabetic patient with retinopathy
Feng Tan, Chengcheng Ding, Xihao Sun
et al.
Diabetic retinopathy (DR) is one of the most common and severe microvascular complications of diabetes, and the leading cause of preventable blindness in working-aged people. Here, we generated an induced pluripotent stem (iPS) cell line using blood-derived cells from a patient with DR. Peripheral blood mononuclear cells (PBMCs) were reprogrammed with Sendai virus.
Glaucoma as Neurodegeneration in the Brain
Chan JW, Chan NCY, Sadun AA
Jane W Chan,1 Noel CY Chan,2 Alfredo A Sadun1,3 1Department of Ophthalmology, Doheny Eye Institute, Pasadena, CA, USA; 2Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong, People’s Republic of China; 3Department of Ophthalmology, University of California, Los Angeles, CA, USACorrespondence: Jane W Chan Tel +1 702 290 9550Fax +1 626 817 4745Email janechan098@gmail.comAbstract: Glaucoma, a group of diseases characterized by progressive optic nerve degeneration that results in irreversible blindness, can be considered a neurodegenerative disorder of both the eye and the brain. Increasing evidence from human and animal studies have shown that glaucoma shares some common neurodegenerative pathways with Alzheimer’s disease (AD) and other tauopathies, such as chronic traumatic encephalopathy (CTE) and frontotemporal dementia. This hypothesis is based on the focal adhesion pathway hypothesis and the spreading hypothesis of tau. Not only has the Apolipoprotein E (APOE) gene been shown to be associated with AD, but also with primary open angle glaucoma (POAG). This review will highlight the relevant literature in the past 20 years from PubMed that show the pathogenic overlap between POAG and AD. Neurodegenerative pathways that contribute to transsynaptic neurodegeneration in AD and other tauopathies might also be similar to those in glaucomatous neurodegeneration.Keywords: primary open-angle glaucoma, tauopathy, amyloid precursor protein, phosphorylated tau, Alzheimer’s disease
Ophthalmology, Neurology. Diseases of the nervous system
Cortical hemodynamic responses induced by low-intensity transcranial ultrasound stimulation of mouse cortex
Yi Yuan, Zhijie Wang, Mengyang Liu
et al.
Ultrasound-mediated neuromodulation is emerging as a key technology for targeted noninvasive brain stimulation, but key insights into its effects and dose-response characteristics are still missing. The purpose of this study is to systematically evaluate the effect of low-intensity transcranial ultrasound stimulation (TUS) on complementary aspects of cerebral hemodynamic. We simultaneously record the EMG signal, local field potential (LFP) and cortical blood flow (CBF) using electrophysiological recording and laser speckle contrast imaging under ultrasound stimulation to simultaneously monitor motor responses, neural activities and hemodynamic changes during the application of low-intensity TUS in mouse motor cortex, using excitation pulses which caused whisker and tail movement. Our experimental results demonstrate interdependent TUS-induced motor, neural activity and hemodynamic responses that peak approximately 0.55s, 1.05s and 2.5s after TUS onset, respectively, and show a linear coupling relationship between their respective varying response amplitudes to repeated stimuli. We also found monotonic dose-response parametric relations of the CBF peak value increase as a function of stimulation intensity and duration, while stimulus duty-cycle had only a weak effect on peak responses. These findings demonstrate that TUS induces a change in cortical hemodynamics and LSCI provide a high temporal resolution view of these changes.
Neurosciences. Biological psychiatry. Neuropsychiatry
Light deprivation reduces the severity of experimental diabetic retinopathy
Christina Thebeau, Sheng Zhang, Alexander V. Kolesnikov
et al.
Illumination of the retina is a major determinant of energy expenditure by its neurons. However, it remains unclear whether light exposure significantly contributes to the pathophysiology of common retinal disease. Driven by the premise that light exposure reduces the metabolic demand of the retina, recent clinical trials failed to demonstrate a benefit for constant illumination in the treatment of diabetic retinopathy. Here, we instead ask whether light deprivation or blockade of visual transduction could modulate the severity of this common cause of blindness. We randomized adult mice with two different models of diabetic retinopathy to 1-3 months of complete dark housing. Unexpectedly, we find that diabetic mice exposed to short or prolonged light deprivation have reduced diabetes-induced retinal pathology, using measures of visual function, compared to control animals in standard lighting conditions. To corroborate these results, we performed assays of retinal vascular health in diabetic Gnat1−/− and Rpe65−/− mice, which lack phototransduction. Both mutants displayed less diabetes-associated retinal vascular disease compared to respective wild-type controls. Collectively, these results suggest that light-induced visual transduction promotes the development of diabetic retinopathy and implicate photoreceptors as an early source of visual pathology in diabetes.
Neurosciences. Biological psychiatry. Neuropsychiatry
Objective Imaging Diagnostics for Dry Eye Disease
Sang Beom Han, Yu-Chi Liu, Karim Mohamed-Noriega
et al.
Traditional diagnostic tests for dry eye disease (DED), such as fluorescein tear film break-up time and the Schirmer test, are often associated with poor reproducibility and reliability, which make the diagnosis, follow-up, and management of the disease challenging. Advances in ocular imaging technology enables objective and reproducible measurement of changes in the ocular surface, tear film, and optical quality associated with DED. In this review, the authors will discuss the application of various imaging techniques, such as, noninvasive tear break-up time, anterior segment optical coherence tomography, in vivo confocal microscopy, meibography, interferometry, aberrometry, thermometry, and tear film imager in DED. Many studies have shown these devices to correlate with clinical symptoms and signs of DED, suggesting the potential of these imaging modalities as alternative tests for diagnosis and monitoring of the condition.
Biosafety of a 3D-printed intraocular lens made of a poly(acrylamide-co-sodium acrylate) hydrogel in vitro and in vivo
Jia-Wen Li, Yi-Jian Li, Xi-Su Hu
et al.
AIM: To assess the biosafety of a poly(acrylamide-co-sodium acrylate) hydrogel (PAH) as a 3D-printed intraocular lens (IOL) material.
METHODS: The biosafety of PAH was first evaluated in vitro using human lens epithelial cells (LECs) and the ARPE19 cell line, and a cell counting kit-8 (CCK-8) assay was performed to investigate alterations in cell proliferation. A thin film of PAH and a conventional IOL were intraocularly implanted into the eyes of New Zealand white rabbits respectively, and a sham surgery served as control group. The anterior segment photographs, intraocular pressure (IOP), blood parameters and electroretinograms (ERG) were recorded. Inflammatory cytokines in the aqueous humor, such as TNFα and IL-8, were examined by ELISA. Cell apoptosis of the retina was investigated by TUNEL assay, and macroPAHge activation was detected by immunostaining.
RESULTS: PAH did not slow cell proliferation when cocultured with human LECs or ARPE19 cells. The implantation of a thin film of a 3D-printed IOL composed of PAH did not affect the IOP, blood parameters, ERG or optical structure in any of the three experimental groups (n=3 for each). Both TNFα and IL-8 in the aqueous humor of PAH group were transiently elevated 1wk post-operation and recovered to normal levels at 1 and 3mo post-operation. Iba1+ macroPAHges in the anterior chamber angle in PAH group were increased markedly compared to those of the control group; however, there was no significant difference compared to those in the IOL group.
CONCLUSION: PAH is a safe material for 3D printing of personal IOLs that hold great potential for future clinical applications.
3D - digitally assisted ocular surgery
Prashant K Bawankule, Shilpi H Narnaware
Immunotoxin-Induced Ablation of the Intrinsically Photosensitive Retinal Ganglion Cells in Rhesus Monkeys
Lisa A. Ostrin, Christianne E. Strang, Kevin Chang
et al.
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.
Neurology. Diseases of the nervous system
FIFTY YEARS OF PROFESSOR V.V. CHERNYKH AS DIRECTOR OF THE NOVOSIBIRSK BRANCH OF THE S. FYODOROV EYE MICROSURGERY FEDERAL STATE INSTITUTION
статья Редакционная
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