Identification of differentially regulated proteins in a patient with Leber's Congenital Amaurosis – a proteomic study

BACKGROUND: To identify the pattern of protein expression in the retina from a patient with Leber's Congenital Amaurosis (LCA) secondary to a mutation in the AIPL1 gene. The retina from one eye of a patient with LCA and 7 control eyes were studied. The tissue was subjected to high resolution two-dimensional gel electrophoresis, image analysis and mass spectrometry, in an effort to identify differentially regulated proteins. RESULTS: In the LCA retina seven protein spots were differentially expressed. Six proteins were significantly up-regulated of which three could be identified as: αA-crystallin, triosephophate isomerase, and an N-terminal fragment of the β-chain of ATP synthase. One protein spot that was down-regulated in the LCA retina was identified as a C-terminal fragment of β-tubulin. CONCLUSION: Retinal tissue in LCA is characterised by an up-regulation of αA-crystallin, triosephosphate isomerase, and ATP synthase (β-chain fragment) and down-regulation of a fragment of β-tubulin. These proteins/protein fragments may play a crucial role for the retinal degeneration processes in LCA and other retinal dystrophies

Retinal oxygen saturation changes progressively over time in diabetic retinopathy.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadPurpose: According to cross-sectional studies, oxygen saturation is elevated in retinal vessels in diabetic patients. We evaluated how retinal oxygenation (metabolic marker), vessel diameters and retinopathy grade (structural markers) change over time in diabetic patients. Design: Prospective cohort study following screening in a hospital setting. Methods: Retinal oximetry images were acquired in 214 patients with the Oxymap T1 oximeter. Imaging was repeated after a median of 3.0 years (range 0.76-6.8 years). Oxygen saturation and vessel diameters were measured in the right eye. Semiquantitative grading of retinopathy according to international guidelines and red lesion count were performed on fundus photographs. Results: Retinopathy grade according to the international semiquantitative grading system was unchanged. Arteriolar saturation increased by 0.75±0.15 percentage points per year of follow-up (p0.44). Conclusions: Oxygen saturation in larger retinal vessels can increase and arteriovenous difference can decrease over time in diabetic patients without any observable changes in retinopathy grade. The results suggest that changes in retinal oxygen saturation may precede progression of diabetic retinopathy or that oxygen saturation is more sensitive to disease progression than retinopathy grade.Icelandic Center for Research Toyota Foundation University of Iceland Research Fund Helga Jonsdottir and Sigurlidi Kristjansson Memorial Fun

Spatial distribution of early red lesions is a risk factor for development of vision-threatening diabetic retinopathy

Aims/hypothesis Diabetic retinopathy is characterised by morphological lesions related to disturbances in retinal blood flow. It has previously been shown that the early development of retinal lesions temporal to the fovea may predict the development of treatment-requiring diabetic maculopathy. The aim of this study was to map accurately the area where lesions could predict progression to vision-threatening retinopathy. Methods The predictive value of the location of the earliest red lesions representing haemorrhages and/or microaneurysms was studied by comparing their occurrence in a group of individuals later developing vision-threatening diabetic retinopathy with that in a group matched with respect to diabetes type, age, sex and age of onset of diabetes mellitus who did not develop vision-threatening diabetic retinopathy during a similar observation period. Results The probability of progression to vision-threatening diabetic retinopathy was higher in a circular area temporal to the fovea, and the occurrence of the first lesions in this area was predictive of the development of vision-threatening diabetic retinopathy. The calculated peak value showed that the risk of progression was 39.5% higher than the average. There was no significant difference in the early distribution of lesions in participants later developing diabetic maculopathy or proliferative diabetic retinopathy. Conclusions/interpretation The location of early red lesions in diabetic retinopathy is predictive of whether or not individuals will later develop vision-threatening diabetic retinopathy. This evidence should be incorporated into risk models used to recommend control intervals in screening programmes for diabetic retinopathy

Similarities and differences in systemic risk factors for retinal artery occlusion and stroke:A nationwide case-control study

BackgroundRetinal artery occlusion (RAO) has been considered a stroke equivalent. This study compares risk factor profiles for thromboembolism among patients with RAO and stroke, respectively.MethodsThis case-control study is based on 5683 RAO patients entered in the Danish National Patient Register between 1st of January 2000 and 31st of December 2018. Cases were matched on sex, year of birth, and age at event with 28,415 stroke patients. The Danish nationwide registries were used to collect information about age, sex, previous diagnoses, and drug prescriptions. Adjusted conditional logistic regression models were used to investigate the association between hypothesised risk factors and the patient outcome.ResultsFor atrial fibrillation, a substantially stronger association to stroke was found, with an odds ratio (OR) of 0.52 (95% CI: 0.47-0.58) when comparing RAO patients with stroke patients. RAO was stronger associated with arterial hypertension, peripheral artery disease, retinal vein occlusion, cataract, and glaucoma with OR's ranging from 1.21-11.70. The identified effect measures reached equivalence or was close to equivalence for diabetes, heart failure, ischemic heart disease, and renal disease.ConclusionThe differences in risk factor profiles between RAO and stroke suggests differences in the pathophysiology of the two diseases. These variations in pathophysiologies between the two diseases may indicate that different interventions are needed to ensure the optimal long-term prognosis for the patients

Intraocular currents, Bernoulli's principle and non-drainage scleral buckling for rhegmatogenous retinal detachment

For many years, it is not fully understood how non-drainage scleral buckling surgery brings about spontaneous reattachment of the detached retina when retinal breaks remain open at the end of surgery. Various explanations have been put forward, but none more interesting than the effect of fluid currents associated with eye movements. One such explanation involved the physics of the Bernoulli’s principle. Daniel Bernoulli was an eighteenth century Swiss mathematician and he described an equation based on the conservation of energy. The sum of pressure energy, potential energy and kinetic energy remains constant. Bernoulli’s equation usually applies to closed system such as the flow of fluid through pipes. When fluid flows through a constriction, the speed of fluid increases, the kinetic energy increases. If there was no change in elevation (potential energy), the increase in kinetic energy must be accompanied by a decrease in pressure energy. In ophthalmic surgery, the Bernoulli’s effect is the basis for venturi pumps that drive vitrectomy and phacoemulsification machines. This essay expounds on how Bernoulli’s effect might be relevant to scleral buckling for retinal detachment repair. In the era when vitrectomy is increasing the primary surgical operation for retinal detachment, the pervasive advice is to emphasise the importance of patient adopting head posture and remaining still postoperatively. The exception is non-drainage scleral buckling surgery. Early postoperative mobilisation may be vital to achieve reattachment

Evaluation of the capacitive behavior of 3D carbon electrodes for sub-retinal photovoltaic prosthesis

Here, we evaluate if microfabricated 3D pyrolytic carbon electrodes are suitable for application in sub-retinal photovoltaic prosthesis. This is done by measuring the charge storage capacity (CSC) and the maximum injectable charge, which indicate if the electrodes allow accumulation of sufficiently high charges in the charge cycle and are able to provide sufficiently fast discharge to stimulate neurons, respectively. The CSC was determined to 10.9 mC/cm2 for carbon pillars and 6.4 mC/cm2 for planar carbon electrodes. These values are comparable with values obtained for state-of-the-art electrode materials applied for retinal stimulation such as iridium oxide (IrOx). The maximum injectable charge was determined from cyclic voltammograms (CV) with values of 1.0 and 1.7 mC/cm2 for planar and pillar carbon electrodes, respectively. The measured contact resistance between carbon and n + doped Si confirms that pyrolytic carbon is a possible candidate for integration as a 3D electrode material on photovoltaic silicon retinal implants. The elemental composition of the fabricated pyrolytic carbon pillars was analyzed by X-ray photoelectron spectroscopy (XPS). The analysis showed that the Al2O3 passivated sample with fabricated pyrolytic carbon pillars only contained aluminum, oxygen and carbon, indicating a successful pyrolysis process without any unwanted elements. The study shows promising potential for pyrolytic carbon as a material for 3D electrodes in retinal, photovoltaic implants. Keywords: Retinal prosthesis, Photovoltaic, 3D electrodes, Pyrolytic carbon, Sub-retinal stimulatio

The Danish registry of diabetic retinopathy

AIM OF DATABASE: To monitor the development of diabetic eye disease in Denmark and to evaluate the accessibility and effectiveness of diabetic eye screening programs with focus on interregional variations. TARGET POPULATION: The target population includes all patients diagnosed with diabetes. Denmark (5.5 million inhabitants) has ~320,000 diabetes patients with an annual increase of 27,000 newly diagnosed patients. The Danish Registry of Diabetic Retinopathy (DiaBase) collects data on all diabetes patients aged ≥18 years who attend screening for diabetic eye disease in hospital eye departments and in private ophthalmological practice. In 2014–2015, DiaBase included data collected from 77,968 diabetes patients. MAIN VARIABLES: The main variables provide data for calculation of performance indicators to monitor the quality of diabetic eye screening and development of diabetic retinopathy. Data with respect to age, sex, best corrected visual acuity, screening frequency, grading of diabetic retinopathy and maculopathy at each visit, progression/regression of diabetic eye disease, and prevalence of blindness were obtained. Data analysis from DiaBase’s latest annual report (2014–2015) indicates that the prevalence of no diabetic retinopathy, nonproliferative diabetic retinopathy, and proliferative diabetic retinopathy is 78%, 18%, and 4%, respectively. The percentage of patients without diabetic maculopathy is 97%. The proportion of patients with regression of diabetic retinopathy (20%) is greater than the proportion of patients with progression of diabetic retinopathy (10%). CONCLUSION: The collection of data from diabetic eye screening is still expanding in Denmark. Analysis of the data collected during the period 2014–2015 reveals an overall decrease of diabetic retinopathy compared to the previous year, although the number of patients newly diagnosed with diabetes has been increasing in Denmark. DiaBase is a useful tool to observe the quality of screening, prevalence, and progression/regression of diabetic eye disease