J. Racine

Dark adaptation is faster in pigmented than albino rats.

Purpose: Previous reports have raised the possibility that, compared to pigmented rats, albino rats might be night blind. The purpose of this study was to reinvestigate this issue by comparing the dark-adaptation process of the pigmented Long-Evans (LE) and albino Sprague Dawley (SD) rats. Methods: Scotopic ERGs obtained from LE and SD rats were recorded following periods of dark adaptation 0.5, 3 and 12 h. Intensity response functions were generated with flashes of white light spanning over a 7 log-unit range with a maximal intensity of 8 cd.s.m−2 in energy. Results: SD rats showed a gradual increase in the amplitude of the scotopic b-wave Vmax (maximal `saturated rod b-wave amplitude) and retinal sensitivity (k) as the duration of the dark-adaptation period increased. In contrast, LE rats did not demonstrate any further significant gain in retinal function (Vmax or k) beyond 30 min of dark-adaptation. Thus for periods of dark-adaptation of 30 min or less, the rod function of the LE rats is superior to that of the SD rats while both strains have comparable retinal functions following 3 h or more of dark-adaptation. Conclusions: Our results indicate that LE and SD rats differ in their rapidity to dark-adapt, a finding that could explain the previous claim that SD rats were night blind. The reduced bio-availability of calcium ions in eyes lacking melanin could explain this difference. Calcium was previously shown to play a key role in retinal adaptation processes.

Complete deficiency of methylenetetrahydrofolate reductase in mice is associated with impaired retinal function and variable mortality, hematological profiles, and reproductive outcomes

Severe deficiency of methylenetetrahydrofolate reductase (MTHFR) with homocystinuria can result in early demise or later-onset neurological impairment, including developmental delay, motor dysfunction, and seizures. We previously characterized BALB/c Mthfr−/−mice as a model for this disorder and have recently backcrossed the disrupted allele onto the C57Bl/6 background to examine the variable phenotypes in MTHFR deficiency. Compared with BALB/c Mthfr−/−mice, C57Bl/6 Mthfr−/−mice have enhanced survival rates (81% vs 26.5%). Four-day-old BALB/c mutant pups had lower body, brain, and spleen weights relative to their wild-type counterparts compared with C57Bl/6 mutants. Pregnant BALB/c Mthfr+/−mice had increased resorptions and embryonic delays compared with wild-type littermates, whereas these outcomes in C57Bl/6 c Mthfr+/−mice were similar to those of wild-type C57Bl/6 mice. BALB/c-mutant pups had altered hematological profiles (higher hematocrit, hemoglobin, and white blood cell counts, with lower platelet counts) compared with C57Bl/6 mutants. Mutants of both strains had similar degrees of hepatic steatosis, hepatic activity of betaine:homocysteine methyltransferase, and altered cerebellar histology. Electroretinograms (ERG) in C57Bl/6 Mthfr−/−mice revealed decreased amplitude of scotopic and photopic waves in 6-week-old mice, with normalized ERGs at 13xa0weeks. Plasma homocysteine was modestly higher in C57Bl/6 compared with BALB/c mice. Our results emphasize the variable presentation of MTHFR deficiency in different genetic backgrounds and suggest that plasma homocysteine is not a predictor of severity. In addition, our novel findings of decreased spleen weights, thrombocytopenia, and impaired retinal function warrant investigation in patients with severe MTHFR deficiency or other forms of homocystinuria.

The photopic ERG of the albino guinea pig (Cavia porcellus) : A model of the human photopic ERG

Altricial rodents such as rats and mice are probably the most widely used animal model in the electroretinogram (ERG) literature. However, while the scotopic responses of these rodents share obvious similarities with that of humans, their photopic electroretinograms are strikingly different. For instance, the photopic ERGs of rats and mice include, when measurable, a minimal a-wave, while the b-wave is of much larger amplitude than that of humans. The purpose of this study is to present the albino guinea pig which is like humans, is a precocial animal, and is a better rodent model of the human photopic ERG. In order to investigate the above, photopic electroretinograms and oscillatory potentials, obtained from guinea pigs and human subjects, were compared. Furthermore, in a subset of animals we injected, intravitreally, selective blockers of the ON- (L-2-amino-4-phosphonobutyric acid: L-AP-4; 10xa0mM) or OFF- (kynurenic acid: KYN; 50xa0mM) retinal pathways in order to mimic similar retinal disorders found in human. Based on our results, we believe that, compared to rats and mice, the photopic (cone-mediated) ERG of the guinea pig clearly represents a superior rodent model of the human photopic ERG.

Structural and functional maturation of the retina of the albino Hartley guinea pig

Purpose Altricial animals, such as rats and mice, are born with their eyes closed, compared to precocial animals, such as guinea pigs and humans, which have their eyes opened at birth. The purpose of this study was to investigate if the retina of guinea pigs (precocial animal) is subjected to a postnatal maturation process similar to that previously reported for rodents. Methods Photopic and scotopic electroretinograms (ERG) and retinal histology were obtained from albino guinea pigs aged P1 to P75. Results Photopic ERG responses reached maximal amplitudes at P5 (a-and b-waves), that is 5xa0days (b-wave) to 10xa0days (a-wave) earlier than scotopic responses. However, the postnatal gain in b-wave amplitude was significantly (Pxa0<xa00.05) more important for the cone (73.38xa0±xa04.4%) signal than for the rod (15.23xa0±xa03.96%), suggesting that the rod function is more mature at birth. Similarly, the short latency photopic oscillatory potential (ie: OP2) reached its maximal value 5xa0days (P10) earlier than its scotopic equivalent (P15), while the long latency OPs (ie: OP3, OP4), reached their maximal values nearly 20xa0days sooner in scotopic condition. Finally retinal histology revealed a thinning of the retina with age, the latter being most pronounced at the level of the ganglion cell layer (GCL). Conclusion Our results thus confirm that despite its relative maturity at birth (compared to rodents), the retina of newborn albino guinea pigs undergoes significant postnatal maturation modifying its structure as well as its function, albeit not as extensive as that previously documented for altricial animals.

Estimating ON and OFF contributions to the photopic hill: normative data and clinical applications

BackgroundWith progressively brighter stimuli, the amplitude of the b-wave of the human photopic electroretinogram (ERG) first increases to a maximal value (Vmax) and then decreases to finally reach a plateau, a phenomenon known as the photopic hill (PH). A mathematical model combining a Gaussian (G) and a logistic (L) growth function was previously proposed to fit this unusual luminance-response curve, where the G and L functions were suggested to represent, respectively, the OFF and ON retinal pathway contributions to the building of the PH.MethodThe PHs of patients presenting stationary diseases affecting specifically the ON (3 CSNB-1) or OFF (4 CPCPA) retinal pathways as well as patients affected with retinitis pigmentosa (14 RP) of different stages or etiology were analyzed using this mathematical model and compared to the PHs of a group of 28 normal subjects.ResultsThe PH of the CSNB-1 patients had a much larger contribution from the G function compared to normal subjects, whereas the opposite was observed for the CPCPA patients. On the other hand, analysis of data from RP patients revealed variable G–L contributions to the building of their PH.ConclusionIn this study, we confirm the previous claim that the luminance-response function of the photopic ERG b-wave can be decomposed into a Gaussian function and a logistic growth function representing, respectively, the OFF and ON retinal pathways. Furthermore, our findings suggest that this mathematical decomposition could be useful to further segregate and potentially follow the progression of retinopathies such as RP.

Spontaneous occurrence of a potentially night blinding disorder in guinea pigs

Several hereditary retinal disorders such as retinitis pigmentosa and congenital stationary night blindness compromise, sometimes exclusively, the activity of the rod pathway. Unfortunately, there are few animal models of these disorders that could help us better understand the pathophysiological processes involved. The purpose of this report is to present a pedigree of guinea pigs where, as a result of a consanguineous mating and subsequent selective breeding, we developed a new and naturally occurring animal model of a rod disorder. Analysis of the retinal function with the electroretinogram reveals that the threshold for rod-mediated electroretinograms (ERGs) is significantly increased by more than 2 log-units compared to that of normal guinea pigs. Furthermore, in response to a suprathreshold stimulus, also delivered under scotopic condition, which yield a mixed cone-rod response in normal guinea pigs, the ERG waveform in our mutant guinea pigs is almost identical (amplitude and timing of a- and b-waves) to that evoked in photopic condition. The above would thus suggest either a structural (abnormal development or absence) or a functional deficiency of the rod photoreceptors. We believe that our pedigree possibly represents a new animal model of a night blinding disorder, and that this condition is inherited as an autosomal recessive trait in the guinea pig population.