ABSTRACT
BACKGROUND: With 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. METHOD: The 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. RESULTS: The 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. CONCLUSION: In 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.
Subject(s)
Color Vision/physiology , Eye Diseases, Hereditary/physiopathology , Genetic Diseases, X-Linked/physiopathology , Models, Theoretical , Myopia/physiopathology , Night Blindness/physiopathology , Retinal Bipolar Cells/physiology , Retinal Degeneration/physiopathology , Retinitis Pigmentosa/physiopathology , Adult , Aged , Electroretinography , Female , Humans , Male , Retinal Cone Photoreceptor CellsABSTRACT
Although a great deal of emphasis has been placed on the vasculopathy that is associated with oxygen-induced retinopathy (OIR), our studies also revealed significant and irreversible structural (retinal histology) and functional (scotopic and photopic electroretinograms) impairments that were significantly more severe in pigmented Long-Evans rats compared to the more commonly used albino Sprague Dawley rats. In the following pages, we will highlight what we have learned about the retinal pathophysiological processes of OIR taking place in strains of both rats with the hope that this will trigger investigations into new therapeutic strategies to complement those geared at preventing the vasculopathy.
Subject(s)
Disease Models, Animal , Hyperoxia/physiopathology , Retina/physiopathology , Retinal Neovascularization/physiopathology , Retinopathy of Prematurity/physiopathology , Animals , Animals, Newborn , Electroretinography , Humans , Infant, Newborn , Oxygen/toxicity , Rats , Retinal Vessels/drug effectsABSTRACT
The neonatal rat is born with its eyes closed and an immature visual system, that some say is equivalent to that of a human fetus at 26 weeks of gestation. From birth, the visual system of the newborn rat will gradually mature, the first manifestation of that being the opening of the eye which usually take place at postnatal day 14. Complete maturation of the retina and visual pathways is normally reached at the end of the first month of life. The neonatal rat model thus represents a unique paradigm to study the normal and abnormal maturation of the primary visual pathways that normally occurs in utero in human subjects. Our laboratory has, over the past decade, developed two animal models of postnatally induced retinopathy, namely the Oxygen-Induced Retinopathy (OIR) that share several common features with the human Retinopathy of Prematurity (ROP) and the Light-Induced Retinopathy that is viewed by some as a valid model of some forms of Retinitis Pigmentosa (RP). The following pages review what is known of the pathophysiological processes taking place and suggest possible therapeutic avenues that could be explored in order to halt the degenerative process.
Subject(s)
Light , Oxygen , Retina/drug effects , Retina/embryology , Visual Pathways/embryology , Animals , Animals, Newborn , Disease Models, Animal , Fetal Development , Humans , Infant, Newborn , Isoprostanes/physiology , Platelet Activating Factor/physiology , Rats , Retinitis Pigmentosa/physiopathology , Retinopathy of Prematurity/physiopathology , Thromboxane A2/physiologyABSTRACT
The ankyrin 33-residue repeating motif, an L-shaped structure with protruding beta-hairpin tips, mediates specific macromolecular interactions with cytoskeletal, membrane, and regulatory proteins. The association between ankyrin and alpha-Na,K-ATPase, a ubiquitous membrane protein critical to vectorial transport of ions and nutrients, is required to assemble and stabilize Na,K-ATPase at the plasma membrane. alpha-Na,K-ATPase binds both red cell ankyrin (AnkR, a product of the ANK1 gene) and Madin-Darby canine kidney cell ankyrin (AnkG, a product of the ANK3 gene) utilizing residues 142-166 (SYYQEAKSSKIMESFK NMVPQQALV) in its second cytoplasmic domain. Fusion peptides of glutathione S-transferase incorporating these 25 amino acids bind specifically to purified ankyrin (Kd = 118 +/- 50 nM). The three-dimensional structure (2.6 A) of this minimal ankyrin-binding motif, crystallized as the fusion protein, reveals a 7-residue loop with one charged hydrophilic face capping a double beta-strand. Comparison with ankyrin-binding sequences in p53, CD44, neurofascin/L1, and the inositol 1,4,5-trisphosphate receptor suggests that the valency and specificity of ankyrin binding is achieved by the interaction of 5-7-residue surface loops with the beta-hairpin tips of multiple ankyrin repeat units.
