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PubMed1993

Phenotypic variation in combined granular-lattice (Avellino) corneal dystrophy.

OBJECTIVE: To describe the phenotypic variation exhibited by members of families with combined granular-lattice (Avellino) corneal dystrophy. SETTING: We examined 40 patients (age range, 12 to 85 years) from six unrelated families with Avellino corneal dystrophy. This included the first individuals to ever be examined near the presumed site of origin in Italy. In addition, one family was the first to trace its origins to Germany rather than to Italy. We studied the phenotypic expression of the disease in the cornea, visual acuities, subjective complaints, complications, treatment, and histologic condition of these individuals. RESULTS: The granular stromal lesions reach their mature quantity and size early in life, and appear as either gray and crumb-shaped deposits or superficial with an annular and planar distribution. The lattice component appears gradually, beginning and maturing later in life. The phenotypic variation within families was found to be substantial. Widely variable proportions of lattice and granular changes were found within single sibships. Visual acuities ranged from 20/20 to 20/400. Recurrent corneal erosions were present but infrequent. Subjective complaints included glare and decreased night vision. Penetrating keratoplasty was required in one individual to restore vision. Histopathologic examination revealed typical amyloid and granular deposits. Granular deposits were found replacing Bowman's membrane and extending to the corneal surface. These deposits probably represent the cause of recurrent erosions. CONCLUSIONS: Combined granular and lattice corneal dystrophy may present with substantial phenotypic variation. The disease can be found in individuals who trace their ancestry to both Italy and Germany, a wider geographic distribution than previously proposed.

Adolescent↗
PubMed1995

The effects of ablation diameter on the outcome of excimer laser photorefractive keratectomy. A prospective, randomized, double-blind study.

OBJECTIVE: To determine the effects of the ablation diameter on the outcome of excimer laser photorefractive keratectomy. DESIGN: Eighty patients were randomized to either a 5.00-mm or a 6.00-mm treatment group and within these groups underwent either a -3.00-diopter (D) or a -6.00-D correction based on their preoperative refraction. A Summit Omnimed excimer laser was used throughout the study. RESULTS: In eyes treated with a 6.00-mm-diameter ablation, the initial hyperopic shift was reduced, with significant differences at 1 week with -3.00-D corrections and at 1 and 4 weeks with -6.00-D corrections (P < .01). At 6 months, the refractive changes were greater and closer to that intended with 6.00-mm-diameter ablations. The predictability of photorefractive keratectomy was significantly improved with 6.00-mm zones, with a reduction in variance of the refractive changes at all stages postoperatively (P < .05 to P < .001). With -3.00-D corrections, objective measurements showed significantly less anterior stromal haze in eyes treated with 6.00-mm zones at 6 months (P < .05). With -6.00-D corrections, haze was significantly reduced at 1, 3, and 6 months in the eyes treated with 6.00-mm zones (P < .05). Five eyes treated with 5.00-mm zones experienced severe regression of the correction, with marked corneal haze and a reduction of 3 or more lines of best corrected Snellen visual acuity at 6 months. No eyes treated with 6.00-mm zones were similarly affected. Computerized measurements of "night" halo were significantly lower in the 6.00-mm treatment groups at 1 week and at 1 and 6 months in the eyes with -3.00-D corrections and at 1 week and at 1 month in the eyes with -6.00-D corrections (P < .05). At 6 months, seven patients treated with 5.00-mm zones complained of severe disturbances of night vision. No eyes in the 6.00-mm group were similarly affected. CONCLUSIONS: Treatment with 6.00-mm ablation diameters precipitated less initial overcorrection, greatly improved the predictability of photorefractive keratectomy, and was associated with a reduction in complications impairing postoperative visual performance.

Adult↗
PubMed1995

Genetic linkage of Wagner disease and erosive vitreoretinopathy to chromosome 5q13-14.

BACKGROUND: Wagner disease and erosive vitreoretinopathy are potentially blinding autosomal dominant diseases that share some similarities with Stickler syndrome. However, both disorders have associated retinal pigment epithelial changes, poor night vision, visual field defects, and abnormal electroretinographic findings, which are not found in families with COL2A1-associated Stickler syndrome. In addition, rhegmatogenous retinal detachments are uncommon in Wagner disease but occur in approximately 50% of patients with either Stickler syndrome or erosive vitreoretinopathy. OBJECTIVES: To identify the chromosomal location of the genes involved in Wagner disease and erosive vitreoretinopathy and to distinguish these conditions genetically from Stickler syndrome. METHODS: Fifteen affected members of a family affected with erosive vitreoretinopathy and 24 affected descendants of the pedigree described by Wagner were genotyped with a set of short tandem repeat polymorphisms distributed across the genome. RESULTS: Significant linkage was observed in each family between the disease phenotype and markers that map to chromosome 5q13-14. The highest lod score for the family affected with erosive vitreoretinopathy was 4.2 and was obtained with marker GATA3H06 (theta = 0). The highest lod score for the family affected with Wagner disease was 5.8 and was obtained with marker D5S815 (theta = 0). A candidate gene (cartilage link protein) that is known to lie near the linked interval was screened for mutations, but none was found in either family. CONCLUSIONS: These data suggest that erosive vitreoretinopathy and Wagner disease are allelic disorders and demonstrate that they are genetically distinct from COL2A1-associated Stickler syndrome.

Base Sequence↗
PubMed1994

Retinitis pigmentosa and related disorders: phenotypes of rhodopsin and peripherin/RDS mutations.

Retinitis pigmentosa comprises a group of clinically variable and genetically heterogeneous inherited disorders of the retina. It is estimated that approximately 1.5 million people throughout the world are affected by this disease. It is a slowly progressive disorder and causes loss of night vision and peripheral visual field in adolescence. It can be inherited through an autosomal dominant, recessive, or X-linked mode; the autosomal dominant form is considered to be the mildest form. Molecular genetic studies on the autosomal dominant disorder have shown that, in some families, genes encoding the rhodopsin and peripherin/RDS map very close to the disease loci identified previously by the systematic linkage analyses. These results, together with the observation that a recessive nonsense mutation in the Drosophila opsin gene causes photoreceptor degeneration, prompted an extensive search for the alterations in the human rhodopsin and peripherin/RDS genes in families with autosomal dominant retinitis pigmentosa. As a result, several distinct rhodopsin and peripherin/RDS mutations have been found in approximately 30% of all autosomal dominant cases. A wide variety of clinical expression of the disorder even within a family with the same mutation, its late onset, slow progression, and cone degeneration clearly suggest that some other factors or genes in addition to rhodopsin are responsible for the phenotypic expression of the disorder. In this article, an attempt is made to highlight some of these recent developments and to correlate the various mutations and the phenotypes.

Eye Proteins↗
PubMed1980

The posterior median eyes of the dinopid spider Menneus.

The posterior median (pm) eyes of the dinopid spider Menneus unifasciatus L. Koch are described and compared with the pm eyes of Dinopis, which are highly specialised for night vision. The lenses of Menneus have F-numbers of 0.72 compared to 0.58 in Dinopis, the distance between receptors is ca. 4.0 microns compared to 20-22 microns for Dinopis, and image quality is matched to receptor spacing. The lens of Menneus is simple, while that of Dinopis comprises two components of different refractive indices (Blest and Land 1977). Receptive segments of the pm eyes of Dinopis are hexagonal in transverse section and those of adjacent cells are tightly contiguous, allowing the possibility of both optical and electrical coupling (Blest 1978). Receptive segments of Menneus are separated from each other by glial processes containing little pigment, and each segment possesses two rhabdomeres on opposite faces of the cell. Rhabdomere volumes undergo a daily cycle similar to that described for Dinopis, but of relatively minor extent. It is shown that the pm eye of Dinopis could have evolved from that of Menneus by a simple series of transformations, and that a gain of two logarithmic units of sensitivity can be attributed to changes in optical design alone.

Animals↗
PubMed1982

Epochal trace elements and evolution.

The use of some trace elements by plants and animals during the evolutionary process has resulted in epochal changes. Noteworthy is the fact that plants (but not animals) needed boron in order to grow stems and roots as they left the seas and became anchored on land. Iodine is plentiful in sea water but rare on land. Therefore, the iodination of tyrosine provided an iodine transport mechanism which allowed for the metamorphosis and the development of warm bloodedness--a great evolutionary advantage. Zinc from clay was needed for the formation of the first primitive nucleic acids and, later, the presence of zinc in the retina provide the enhanced night vision of the nocturnal predators--a natural advantage. Hence, boron, iodine and zinc can be termed epochal trace elements. Inquiry should be directed towards the possible roles of other trace elements, which may have been epochal in evolution.

Animals↗
PubMed1983

Influence of low magnetic-field-strength variations on the retina and pineal gland of quail and humans.

Recently, Schulten postulated on the basis of his experiments and quantum-mechanical calculations that variations of the strength of the earth's magnetic field may influence reactions in biological systems. In this paper groups of birds were subjected to different variations of low magnetic-field strength. The influence of these variations on the enzyme hydroxyindol-O-methyl transferase (HIOMT) was determined. HIOMT is unique to the retina and the pineal gland and seems to be involved in regulation of light-adaptation processes. A significant effect was found, which can be interpreted as being in agreement with Schulten's theory. These observations were further supported by our examination of the influence of magnetic field variation on human night-vision acuity. Whereas the magnetic influence on the avian retina may be interpreted in connection with navigation, the importance for the human retina remains to be elucidated.

Acetylserotonin O-Methyltransferase↗
PubMed2001

Rigid gas-permeable contact lens fitting in LASIK patients for the correction of multifocal corneas.

BACKGROUND: Laser in situ keratomileusis (LASIK) has recently become the most commonly performed refractive surgery procedure. Results are promising in correcting low to moderate myopia. Most complications occur during the surgeon's learning curve. One of the complications is a decentration of the ablated area that causes monocular diplopia and a nocturnal halo phenomenon due to a multifocality of the corneal surface overlying the entrance pupil. The corneal shape is significantly altered after LASIK. We evaluate the efficacy of rigid gas-permeable contact lens designs and fitting techniques used in eight eyes with multifocal LASIK ablations to correct haloes and impaired night vision complaints. METHODS: We used large-diameter tetra-curved rigid gas-permeable (RGP) contact lenses for visual recovery in eight eyes of seven LASIK patients. We used the power on the transition zone of the corneal topographic map, 0.2 mm outside the ablated refractive area, for selection of the back optic zone radius of the RGP contact lenses. Procedures for lens fitting are described. Visual acuity (high-contrast logarithm of the minimum angle of resolution, LogMAR) was measured before- and 6 months after contact lens fitting. RESULTS: Large-diameter tetra-curve RGP lenses with a mean diameter of 11.85 (SD 0.16) mm were successfully used in LASIK patients with multifocal corneas. Mean best spectacle-corrected visual acuity was +0.3 LogMAR (SD 0.19; in Snellen equivalent, 20/40) and improved significantly with the contact lenses to +0.08 LogMAR (SD 0.11; in Snellen equivalent, 20/25, P=<0.01). During the follow-up period of 16.7 months, the average daily wearing time of the lenses was 12.5 h. Contact lenses with a standard geometry were not useful due to excessive movement and inadequate centration. CONCLUSIONS: Contact lenses with large diameters, in combination with selection of the back optic zone radius 0.2 mm peripheral of the refractive ablation zone, facilitate contact lens fitting to restore best-corrected visual acuity in LASIK patients with multifocal corneas.

Adult↗
PubMed2006

Relative suppression of the sodium-dependent Vitamin C transport in mouse versus human lens epithelial cells.

Vitamin C is a major antioxidant and UV absorbent in the human lens. In the rodent lens, the levels are very low for unknown reasons. Searching for clues to explain this suppression, we investigated the comparative uptake of Vitamin C in cultured human and mouse lens epithelial cells. When compared to human HLE-B3 lens epithelial cells, (14)C-ASA uptake was 4- to 10-fold impaired in confluent mouse lens 17EM15 (p < 0.0001) and 21EM15 (p < 0.001) cells, respectively. High glucose concentrations reduced the uptake by 30-50% in all cells (p < 0.005). Incubation of cells with 6-deoxy-6-fluoro-ascorbic (F-ASA), i.e. a probe specific for the sodium-dependent Vitamin C uptake (SVCT2), revealed a 10-fold uptake suppression into mouse 17EM15 relative to human HLE-B3 and JAR choriocarcinoma cells (a control), that could be overcome by overexpressing hSVCT2 using two different promoter constructs. The relative Vitamin C uptake differences suggest either low expression of SVCT2, molecular differences between the transporters themselves or their biological regulation, since a recent study has shown that exogenous feeding of ascorbic acid to rats increased only modestly lenticular uptake (Mody et al., Acta Ophthalmol Scand 83: 228-223, 2005). Elucidation of the mechanism by which SCVT2 activity is suppressed in mouse lens may help unravel a major question of evolutionary significance for night vision in nocturnal animals.

Amino Acid Sequence↗
PubMed1981

Electrophysiologic changes in chronic pars planitis.

We studied 13 patients, six males and seven females, ranging in age from 14 to 53 years, with chronic pars planitis and a form of secondary retinal degeneration. All had experienced visual blurring but none had significant pain. Nine of the 13 had some disturbance in night vision. Visual acuity had decreased in three patients (in one because of cataract, in one because of cystoid macular degeneration, and for unknown reasons in the third), increased in two patients (because of improvement in cystoid macular edema), and remained stable in eight. There were electrophysiologic abnormalities, consisting of delayed B-wave implicit time, abnormal response to 30-Hz flicker, and reduced B-wave oscillations, in almost every patient. Our finding suggested that pars planitis is a vitreoretinal disorder rather than an inflammatory disease of the uveal tract.

Adolescent↗
PubMed1989

Tolerability of the synthetic retinoid Fenretinide (HPR).

Fenretinide, N-(4-hydroxyphenyl)retinamide (HPR), is a synthetic retinoid which has been proven effective in inducing cell differentiation and in inhibiting carcinogen induced mammary tumors in rodents. Because of its efficacy and low toxicity in animals, HPR has been proposed for chemopreventive evaluation in humans. Thus, a randomized trial has been conducted to select a dose which can be administered over a lengthy period of time and with acceptable toxicity. The retinoid was administered orally to patients already operated on for breast cancer in daily doses of 100, 200 and 300 mg for 6 months and subsequently at 200 mg for another 6 months. No acute toxicity was found. Dermatological toxicity was minimal and no liver function abnormalities were observed. Nausea and headaches were infrequent and always mild. Menstrual irregularities were recorded with similar frequency in the treatment and placebo groups and appeared to be more age related than drug dependent. After 6 months of treatment one of 25 patients taking 300 mg HPR daily experienced impaired night vision, confirmed by the electroretinogram, and resolved by interruption of treatment. Because the 300 mg daily dose is possibly associated with impaired dark adaptation, the recommended dose for chemoprevention trials of HPR is 200 mg per day.

Adult↗
PubMedDate not supplied

Results and recommendations from the helicopter EMS pilot safety survey 2005.

INTRODUCTION: In 2005, the Pilot Safety Study Group (PSSG), consisting of members of the Association of Air Medical Services Research Committee, wrote, distributed, and analyzed a survey of helicopter pilots regarding their knowledge, attitude, and perspectives on safety in the field of air medical transport. METHODS: The Pilot Safety Survey 2005 (PSS2005) was based on another survey--one that was sponsored by Helicopter Association International (HAI) and National EMS Pilots Association (NEMSPA) and administered to pilots in 2001. The PSS2005 pared questions down so that the survey could be completed in 15 minutes on the internet, and the answers were organized in a manner to simplify analysis. An electronic link to the survey was distributed in a non-randomized fashion to HEMS pilots using the mailing lists of various operators and HEMS programs. Questions were clustered into eight groupings of safety, with a majority of responses being categorical, lending themselves to cross-tabulations. RESULTS: The information gathered indicated that Helicopter EMS (HEMS) pilots are very experienced, with the average pilot logging 6,625 flight hours. Collectively, they took responsibility for HEMS accidents; with 92% of total respondents citing "pushing weather minimums" and 82% citing "pilot decision making" as the main reasons for crashes. Crew resource management (CRM) was well appreciated by the pilots; there appeared to be a positive correlation with programs that offer their employees CRM and the pilots' general perspective on safety. The survey was also clear that amongst 40% of the respondents, mission-oriented training needs improvement, and 74% responded that more realistic training in flight simulators would improve safety overall. Finally, 57% of the pilots both desired night vision goggles or devices (NVG/NVD) and believed that their usage would improve safety in the field of air medical transport (55% vs 45%, P = .0025). CONCLUSIONS: Although the recommendations from the PSS2005 are lacking in definite evidence for a decrease in HEMS crashes, we consider the direct input from pilots as critical in the absolute elimination of crashes in Helicopter EMS (Vision Zero). Pilots are, after all, the very ones held responsible for HEMS crashes. Based on these findings, the PSSG hopes that the HEMS community will incorporate the following recommendations into their standard practices. We recommend that all HEMS operators have annual and regular CRM training. We recommend that all HEMS pilots have annual and regular training in realistic flight simulators. Finally, we recommend that all HEMS aircraft be in possession of NVGs, and if this is not possible (eg, light pollution from a highly urbanized region or cost-benefit issues), then to have annual and regular mission-oriented nighttime training.

Adult↗
PubMed2006

Age-related changes in sympathetic neurotransmission in rat retina and choroid.

While age-related night vision loss and age-related macular degeneration are well characterized, less is known about the normal aging process in the retina and choroid. The purpose of this study was to ascertain whether dopamine beta-hydroxylase (DBH), beta1- and beta2-adrenergic receptor gene and protein expression are altered in the retina and choroid with age. The retina and choroid were dissected from F344xBNF1 hybrid rats aged 8, 22, and 32 months. Real-time PCR and Western blot analysis were conducted to determine steady-state mRNA and protein expression. Immunohistochemistry (IHC) was conducted to localize DBH protein expression in the retina. DBH protein expression was substantially decreased with age in the retina, particularly in the outer nuclear layer, with no changes in DBH expression noted in the choroid. There was a significant increase in beta1-adrenergic receptor protein expression in retinal samples at 22 months, while beta2-adrenergic receptor protein expression was not affected by age. Decreased expression of DBH with age in the retina could lead to reduced production of norepinephrine, potentially resulting in an increase of beta1-adrenergic receptor expression due to denervation supersensitivity. Gene expression for DBH, beta1- and beta2-adrenergic receptors were observed to peak at 22 months and return to baseline levels by 32 months of age in the choroid. Our findings suggest that the retina may be more sensitive to age-related loss of sympathetic neurotransmission than the choroid, which may partially explain normal age-related vision loss in the elderly.

Aging↗
PubMed2004

Laser in situ keratomileusis for myopia and the contrast sensitivity function.

PURPOSE: To characterize the clinical effects of laser in situ keratomileusis (LASIK) on the cornea and visual performance by the contrast sensitivity function (CSF). SETTING: Clinique d'Ophtalmologie IRIS, Laval, Quebec, Canada. METHODS: Thirty-four patients aged 18 to 50 years volunteered for this prospective study. All patients had bilateral LASIK to correct myopia between -1.00 and -6.75 diopters (D) and refractive astigmatism less than 2.50 D. The mean spherical equivalent (SE) refractive error in the 68 eyes was -3.93 D +/- 1.67 (SD). A Hansatome microkeratome (Bausch & Lomb) and a Technolas 217C excimer laser (Bausch & Lomb) driven by the PlanoScan program were used. The monocular CSF for spatial frequencies of 3, 6, 12, and 18 cycles per degree (cpd) for both day and night vision simulations were made with a CSV-1000E system (Vector Vision) before and 1 month and up to 9 months after LASIK. All patients wore their best spectacle correction for the baseline CSF. RESULTS: The group (n = 68) averaged preoperative and postoperative CSFs did not differ at 1 month (analysis of variance [ANOVA], P>.05). In a subgroup of 11 eyes that had corneal microstriae, however, there was a significant reduction in the photopic and mesopic CSF at 6, 12, and 18 cpd (ANOVA, P<.05) despite normal Snellen visual acuities. The CSF normalized in 6 to 9 months as the microstriae became less visible. CONCLUSIONS: Subtle central corneal microstriae after LASIK can reduce the baseline CSF at medium to high spatial frequencies even with 20/20 visual acuity. The CSF normalizes as the microstriae fade over time.

Adolescent↗
PubMed2004

Miotic effect of brimonidine tartrate 0.15% ophthalmic solution in normal eyes.

PURPOSE: To evaluate the effect of brimonidine tartrate 0.15% ophthalmic solution (Alphagan P) on pupil diameter in eyes of healthy adults under different luminance conditions. SETTING: Center for Refractive Surgery, Ophthalmology Service, Department of Surgery, Walter Reed Army Medical Center, Washington, DC, USA. METHODS: Using a Colvard pupillometer, the pupil diameter was measured in 15 eyes of 15 healthy adults under 3 luminance conditions (scotopic, mesopic, photopic). The luminance of the room was measured using the Minolta LS-110 Luminance Meter. Pupil diameter was remeasured using the same technique 30 minutes, 4 hours, and 6 hours after administration of 1 drop of brimonidine tartrate 0.15% ophthalmic solution. RESULTS: Under scotopic conditions (luminance 0.0 candelas [cd]/m(2)), the pupil diameter decreased by 1.0 mm or more in 100%, 87%, and 60% of eyes at 30 minutes, 4 hours, and 6 hours, respectively (P<.005); under mesopic conditions (luminance 0.2 cd/m(2)), in 93%, 73%, and 40% of eyes, respectively (P<.005); and under photopic conditions (luminance 150.2 cd/m(2)), in 73%, 87%, and 67% of eyes, respectively (P<.005). CONCLUSIONS: Brimonidine tartrate 0.15% ophthalmic solution produced a significant miotic effect under all 3 luminance conditions. The reproducible miotic effect under scotopic and mesopic conditions may help postoperative refractive patients who report night-vision difficulties related to a large pupil.

Adrenergic alpha-Agonists↗
PubMed2005

Excimer laser photorefractive keratectomy for hyperopia: 7.5-year follow-up.

PURPOSE: To report the results of a long-term prospective study to evaluate refractive stability and safety of hyperopic photorefractive keratectomy (H-PRK). SETTING: Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom. METHODS: Twenty-one patients (49%) (40 eyes) of cohort of 43 patients who participated in 1 of the first clinical trials of H-PRK were assessed at a mean follow-up of 90.7 months (range 62 to 106 months). The H-PRK was performed using a Summit Technology Apex Plus Excimer laser (Summit Technology, Inc.). The mean preoperative spherical equivalent refraction (SEQ) was +4.70 diopters (D) (range +2.00 to +7.50 D). Patients were allocated to 1 of 4 treatment groups based on their preoperative refraction and received 1 of the following spherical corrections: +1.50 D, +3.00 D, +4.50 D, or +6.00 D. RESULTS: At 7.5 years, the refractive correction remained stable with a mean difference in SEQ between 1 year and 7.5 years of +0.28 D. The mean manifest SEQ was +0.83 D (range +5.00 to -3.00 D). Sixty-seven percent of eyes having corrections of +1.50 D and +3.00 D were within +/-1.00 D of the predicted correction. Predictability was poorer with +4.50 D and +6.00 D corrections, with 40% of eyes within +/-1.00 D of that expected. An improvement in uncorrected near acuity was achieved in 35 eyes (87.5%), and 35 eyes (87.5%) showed an improvement in uncorrected distance acuity from preoperative levels. Best spectacle-corrected visual acuity (BSCVA) was unchanged or improved from preoperative values in 25 eyes (62.5%). Three eyes (8%) lost 2 lines of Snellen BSCVA, which in 2 cases was attributable to cataract formation. A peripheral ring of haze, 6.5 mm in diameter, appeared in most eyes. Its intensity was greatest at 6 months and then diminished with time. In 10 eyes (25%), remnants of the haze ring were evident at 7.5 years and subepithelial iron rings, 6.5 mm in diameter were evident in 26 eyes (70%). No patient complained of night-vision problems and no eye developed ectasia. CONCLUSIONS: In H-PRK, refractive stability achieved at 1 year was maintained up to 7.5 years with no evidence of hyperopic shift, diurnal fluctuation, or late regression. Peripheral corneal haze decreased with time but was still evident in a number of eyes at the last follow-up visit.

Adult↗
PubMed2024

Retinal Proteome Profiling of Inherited Retinal Degeneration Across Three Different Mouse Models Suggests Common Drug Targets in Retinitis Pigmentosa.

Inherited retinal degenerations (IRDs) are a leading cause of blindness among the population of young people in the developed world. Approximately half of IRDs initially manifest as gradual loss of night vision and visual fields, characteristic of retinitis pigmentosa (RP). Due to challenges in genetic testing, and the large heterogeneity of mutations underlying RP, targeted gene therapies are an impractical largescale solution in the foreseeable future. For this reason, identifying key pathophysiological pathways in IRDs that could be targets for mutation-agnostic and disease-modifying therapies (DMTs) is warranted. In this study, we investigated the retinal proteome of three distinct IRD mouse models, in comparison to sex- and age-matched wild-type mice. Specifically, we used the Pde6&#x3b2;Rd10 (rd10) and RhoP23H/WT (P23H) mouse models of autosomal recessive and autosomal dominant RP, respectively, as well as the Rpe65-/- mouse model of Leber's congenital amaurosis type 2 (LCA2). The mice were housed at two distinct institutions and analyzed using LC-MS in three separate facilities/instruments following data-dependent and data-independent acquisition modes. This cross-institutional and multi-methodological approach signifies the reliability and reproducibility of the results. The large-scale profiling of the retinal proteome, coupled with in&#xa0;vivo electroretinography recordings, provided us with a reliable basis for comparing the disease phenotypes and severity. Despite evident inflammation, cellular stress, and downscaled phototransduction observed consistently across all three models, the underlying pathologies of RP and LCA2 displayed many differences, sharing only four general KEGG pathways. The opposite is true for the two RP models in which we identify remarkable convergence in proteomic phenotype even though the mechanism of primary rod death in rd10 and P23H mice is different. Our data highlights the cAMP and cGMP second-messenger signaling pathways as potential targets for therapeutic intervention. The proteomic data is curated and made publicly available, facilitating the discovery of universal therapeutic targets for RP.

Animals↗
PubMed2005

Effects of ambient lighting on visual discrimination, forward masking and attentional facilitation.

Differences between neural processing underling day and night vision occur at initial transduction steps. However, comparison of a visual task performance in photopic versus scotopic situations has an intrinsic problem: ambient light levels directly affect the contrast between stimuli and background. By using a simple but innovative method, we were able to maintain the stimuli/background contrast in order to appropriately evaluate the effects of ambient lighting on visual discrimination, attentional facilitation and forward masking. Our results revealed that ambient light levels does not affect spatial accuracy in central vision, but peripheral stimuli are more rapidly recognized when presented in photopic conditions. Additionally, our data suggest that ambient lighting do not unbalance the opposing effects of attentional facilitation versus forward masking. Modulation of cell coupling that takes place in the retina triggered by ambient light levels may underlie differences in visual discrimination in photopic and scotopic conditions.

Adult↗