Purpose
We investigate how type 2 diabetes (T2DM) and diabetic retinopathy (DR) affect color vision (CV) and mfERG implicit time (IT), whether CV and IT are correlated, and whether CV and IT ...abnormality classifications agree.
Methods
Adams desaturated D-15 color test, mfERG, and fundus photographs were examined in 37 controls, 22 T2DM patients without DR (NoRet group), and 25 T2DM patients with DR (Ret group). Color confusion score (CCS) was calculated. ITs were averaged within the central 7 hexagons (central IT; ≤4.5°) and outside this area (peripheral IT; ≥4.5°). DR was within (DRIN) or outside (DROUT) of the central 7 hexagons. Group differences, percentages of abnormalities, correlations, and agreement were determined.
Results
CCS was greater in the NoRet (
P
= 0.002) and Ret (
P
< 0.0001) groups than in control group. CCS was abnormal in 3, 41, and 48 % of eyes in the control, NoRet, and Ret groups, respectively. Ret group CV abnormalities were more frequent in DRIN than in DROUT subgroups (71 vs. 18 %, respectively;
P
< 0.0001). CCS and IT were correlated only in the Ret group, in both retinal zones (
P
≤ 0.028). Only in the Ret group did CCS and peripheral IT abnormality classifications agree (72 %;
P
< 0.05).
Conclusion
CV is affected in patients with T2DM, even without DR. Central DR increases the likelihood of a CV deficit compared with non-central DR. mfERG IT averaged across central or peripheral retinal locations is less frequently abnormal than CV in the absence of DR, and these two measures are correlated only when DR is present.
Aims: To study the effects of two commonly used pre-amplifier filtering bandwidths on normal multifocal electroretinogram (mfERG) responses and their comparative abilities to detect retinal disease. ...Methods: 103 standard mfERGs were recorded simultaneously in two channels with different pre-amplifier settings (10–100 Hz and 10–300 Hz) from one eye of each of 20 normal subjects, 17 diabetics with non-proliferative diabetic retinopathy (NPDR), and 12 diabetics without retinopathy. Signal to noise ratios (SNR) of the normal subjects’ first order mfERGs were compared between channels. All subjects’ amplitudes and implicit times were derived using a “template stretching” method. For comparison, implicit time was also measured using a “template sliding” method. mfERG amplitudes and implicit times were compared between the channels and among subject groups. Results: Normal mean amplitudes and implicit times were similar for the two channels. However, normal 10–100 Hz recordings had significantly higher SNR and lower intersubject variability than 10–300 Hz recordings. In NPDR, the 10–100 Hz channel identified significantly more implicit time and amplitude abnormalities. In the diabetics without retinopathy, 10–100 Hz filtering identified significantly more implicit time abnormalities than 10–300 Hz filtering. For both filter settings, diabetic implicit times were more often abnormal than amplitudes. The 10–100 Hz channel was superior for both implicit time measurements. Conclusion: Standard mfERGs recorded from normal eyes and filtered 10–100 Hz contain less noise, higher SNR, and less intersubject variability than those filtered at 10–300 Hz. This underlies the finding that the 10–100 Hz filter setting identifies more retinal dysfunction than the 10–300 Hz setting.
To examine the potential of abnormal mfERGs to predict the development of diabetic retinopathy at corresponding retinal locations 1 year later.
One eye of 11 diabetic patients with nonproliferative ...diabetic retinopathy (NPDR) and 11 diabetic patients without retinopathy were retested 12 months after initial testing. At each time, mfERGs were recorded from 103 retinal locations, and fundus photographs were taken within 1 month of each recording. Local mfERG implicit times were measured and their z-scores were calculated based on results obtained from 20 age-matched control subjects. mfERG abnormalities were defined as z-scores of 2 or more for implicit time and z-scores of -2 or less for amplitude (P < or = 0.023). mfERG z-scores were mapped onto fundus photographs, and the relationship between baseline abnormal z-scores and new retinopathy at follow-up was examined.
New retinopathy developed in 7 of the eyes with NPDR after 1 year. In these eyes, 70% of the mfERGs in areas of new retinopathy had abnormal implicit times at baseline. In contrast, only 24% of the responses in regions that remained retinopathy free were abnormal at baseline. Relative risk of development of new retinopathy over 1 year in the areas with abnormal baseline mfERG implicit times was approximately 21 times greater than that in the areas with normal baseline mfERGs (odds ratio = 31.4; P < 0.001). Eyes without initial retinopathy did not develop new retinopathy within the study period, although 4 of these 11 eyes had abnormal implicit times at baseline. mfERG implicit times tended to be more delayed at follow-up than at baseline in NPDR eyes, but not in eyes without retinopathy and control eyes. mfERG amplitudes had no predictive power.
Localized functional abnormalities of the retina reflected by mfERG delays often precede the onset of new structural signs of diabetic retinopathy. Those functional abnormalities predict the local sites of new retinopathy observed 1 year later.
The hypothalamo-neurohypophysial system (HNS) is a brain peptidergic neurosecretory apparatus which is composed of arginine vasopressin (AVP) and oxytocin (OXT) magnocellular neurones and their ...neuronal processes in the posterior pituitary (PP). In response to specific stimuli, AVP and OXT are secreted into the systemic circulation at the neurovascular interface of the PP, where they act as hormones, but they can also behave as neurotransmitters when released at the somatodendritic compartment or by axon collaterals to other brain regions. Because these peptides are crucial for several physiological processes, including fluid homoeostasis and reproduction, it is of great importance to map the HNS connectome in its entirety in order to understand its functions. In recent years, advances in imaging technologies have provided considerable new information about the HNS. These approaches include the use of reporter proteins under the control of specific promoters, viral tracers, brain-clearing methods, genetically encoded indicators, sniffer cells, mass spectrometry imaging, and spatially resolved transcriptomics. In this review, we illustrate how these latest approaches have enhanced our understanding of the structure and function of the HNS and how they might contribute further in the coming years.
To study retinal dysfunction in diabetes and early nonproliferative diabetic retinopathy (NPDR) using a new method to analyze local multifocal electroretinogram oscillatory potentials (mfOPs).
One ...eye of each of 26 normal subjects, 16 diabetic subjects without retinopathy (NoR), and 16 diabetic subjects with early NPDR was examined. Slow-flash multifocal electroretinograms (sf-mfERGs) were recorded from the central 45 degrees, and stereo fundus photographs of the diabetic eyes were taken. The first-order (K1), induced first-order (K1i), and second-order (K2) response components were extracted from each retinal location, and K1i and K2 were added to create Ks2. Responses from 35 contiguous areas were digitally filtered 90 to 225 Hz to isolate the mfOPs. The signal-to-noise ratio (SNR) of the mfOPs was calculated, and abnormality was defined as SNR below the fifth percentile of the normal subjects.
Combining the K1i and K2 components to form Ks2 before isolation of the mfOPs by digital filtering increased the SNR. Mean Ks2 and K1 mfOP SNRs were abnormal in 25% and 19% of the NoR eyes, respectively, and both were abnormal in 62% of the NPDR eyes. The retinal distributions of the local Ks2 and K1 mfOP abnormalities overlapped, but they differed. Furthermore, local Ks2 mfOP abnormalities were preferentially associated with retinal sites containing NPDR but K1 mfOP abnormalities were not.
The cells that contribute to the generation of local mfOPs are affected by diabetes and, to a greater degree, by early NPDR. The results suggest that fast adaptive mechanisms influencing the mfOPs are most abnormal at retinal sites containing NPDR.
To formulate a model to predict the location of the onset of diabetic retinal edema (DE) in adults with diabetic retinopathy (DR), at risk for DE.
In all, 46 eyes from 23 patients with DR were ...included. Subjects were followed semiannually until DE developed or the study concluded. The presence or absence of DE within the central 45 ° at the final visit was the outcome measure, and data from the prior visit were used as baseline. A logistic regression model was formulated to assess the relationship between DE development and: multifocal electroretinogram (mfERG) implicit time (IT) Z-score, mfERG amplitude (Amp) Z-score, sex, diabetes duration, diabetes type, blood glucose, HbA1c, age, systolic (SBP) and diastolic blood pressure, and grade of retinopathy. A total of 35 retinal zones were constructed from the mfERG elements and each was graded for DE. Data from 52 control subjects were used to calculate the maximum IT and minimum Amp Z-scores for each zone. Receiver operating characteristic curves from a fivefold cross-validation were used to determine the model's predictive properties.
Edema developed in 5.2% of all retinal zones and in 35% of the eyes. The mfERG Amp, mfERG IT, SBP, and sex were together predictive of edema onset. Combined, these factors produce a model that has 84% sensitivity and 76% specificity.
Together mfERG, SBP, and sex are good predictors of local edema in patients with DR. The model is a useful tool for assessing risk for edema development and a candidate measure to evaluate novel therapeutics directed at DE.
To formulate and test a model to predict the development of local patches of nonproliferative diabetic retinopathy (NPDR), based on multifocal electroretinogram (mfERG) implicit times and candidate ...diabetic risk factors.
mfERGs and fundus photographs were obtained from 28 eyes of 28 diabetic patients during an initial and 12-month follow-up examination. mfERG implicit times were derived at 103 locations using a template-stretching method, and a z-score was calculated in comparison with 20 age-matched normal subjects. Thirty-five nonoverlapping retinal zones were constructed by grouping two to three adjacent stimulated locations, and each zone was assigned the maximum z-score within it. Zones containing initial retinopathy were excluded from further analysis. The probability that new retinopathy would develop in the remaining zones by the follow-up examination was modeled based on the mfERG implicit time z-score for the zone and other candidate diabetic risk factors determined during the initial visit. Data collected from four previously untested diabetic subjects and the other eye of eight previous subjects during their second year follow-up were used to test the predictive model.
After 1 year, new retinopathy developed in 11 of the 12 NPDR eyes and 1 of the 16 eyes without initial retinopathy. After accounting for the correlation among zones within each eye, a predictive model was formulated with the variables mfERG implicit time, duration of diabetes, presence of retinopathy (NPDR or no retinopathy), and blood glucose level at initial visit. The area under the receiver operating characteristic (ROC) curve of this multivariate model is 0.90 (P <0.001). The predictive model has an expected sensitivity of 86% and a specificity of 84%, which was verified by the test data.
The development of diabetic retinopathy over a 1-year period can be well predicted by a multivariate model. The inclusion of local mfERG implicit times allowed the model to identify the specific sites of future retinopathy.
To examine the mechanism(s) of interferon (IFN) induced expression of major histocompatibility complex (MHC) class 1 molecules on the human retinoblastoma cell line, Y-79.
Y-79 cells were incubated ...in the presence of IFN-alpha, -beta, and -gamma. Y-79 cell expression of MHC class 1 molecules was measured by flow cytometric analysis. HLA-B7 and oncogene transcription were evaluated by Northern blot analysis and nuclear runoff transcription assays.
IFN-gamma increased MHC-class 1 antigen expression and induced a fivefold increase in its transcription rate. Posttranscriptionally, IFN-beta and -gamma increased steady state messenger RNA for the HLA-B7 gene. These effects were not associated with down regulation of N-myc oncogene nuclear transcription. Moreover, dexamethasone did not affect the IFN-gamma induced expression of MHC-class 1 molecules.
Both transcriptional and posttranscriptional mechanisms are implicated in the modulation of class 1 molecule expression by IFN. In addition, this modulation is not associated with down regulation of N-myc oncogene expression. Spontaneous or IFN-gamma induced MHC class 1 antigen expression in retinoblastoma Y-79 cells is resistant to glucocorticoid hormones.
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