Light-induced changes of extracellular ions and volume in 
the isolated chick retina–pigment epithelium preparation

Dmitriev, Andrey V.; Govardovskii, V. I.; Schwahn, Hartmut; Steinberg, Roy H.

doi:10.1017/s095252389916615x

Cited by 67 publications

(61 citation statements)

References 37 publications

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“…It is also true that brain cells swell, with reduction in volume of the ECS under normal conditions of neuronal activity, and many pathophysiological conditions, including ischemia and anoxia (39). ECS can also enlarge under some normal physiological conditions (40,41). Indeed, changes in ECS volume may be more common than supposed, because most experiments are not instrumented to record such variations.…”

Section: Resultsmentioning

confidence: 99%

Changes in brain cell shape create residual extracellular space volume and explain tortuosity behavior during osmotic challenge

Chen

Nicholson

2000

Proc. Natl. Acad. Sci. U.S.A.

123

115

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Diffusion of molecules in brain extracellular space is constrained by two macroscopic parameters, tortuosity factor and volume fraction ␣. Recent studies in brain slices show that when osmolarity is reduced, increases while ␣ decreases. In contrast, with increased osmolarity, ␣ increases, but attains a plateau. Using homogenization theory and a variety of lattice models, we found that the plateau behavior of can be explained if the shape of brain cells changes nonuniformly during the shrinking or swelling induced by osmotic challenge. The nonuniform cellular shrinkage creates residual extracellular space that temporarily traps diffusing molecules, thus impeding the macroscopic diffusion. The paper also discusses the definition of tortuosity and its independence of the measurement frame of reference.diffusion ͉ lattice ͉ volume transmission ͉ cell swelling and shrinkage ͉ numerical simulation M any biological processes involve diffusion of substances through a disordered heterogeneous medium. Diverse examples are intracellular signaling (1), intercellular signaling (2), volume transmission (3, 4), and drug delivery (5, 6). The rapid increase in the use of diffusion-weighted MRI has raised further issues about diffusion in tissues (7). In approaching such problems, two essential parameters are the extracellular space (ECS) volume fraction ␣, the volume ratio of the ECS compared to the whole tissue, and the tortuosity , a measure of how diffusing molecules are hindered by cellular obstructions. Recent studies by using osmotic challenge in brain tissue (8, 9) have shown a complex relation between these two parameters. In this paper, we apply the mathematical technique of homogenization to show that changes in cell shape provide an explanation for osmotic data and are likely to be applicable in a much wider context.To quantify diffusion in a complex biological medium, it is necessary to apply the diffusion equation through the use of some macroscopically effective properties, such as the local average concentration, ͗C͘, and the apparent (or effective) diffusion coefficient, D*. Such macroscopic formulations have been applied successfully in the ECS of brain tissues (8-15). When discussing the ECS, 2 is frequently defined as the ratio between the diffusion coefficient, D, of a given molecule in a bulk liquid and the apparent diffusion coefficient D* of the same molecule in the ECS,although other definitions have been used. Furthermore, some authors (16-18) include terms for viscosity of the ECS and hydrodynamic interaction of the diffusing molecule in their definition of ; we exclude such factors here, to focus on the relationship between geometry and tortuosity, but briefly discuss them later in the paper and in the Appendix, which also comments on the independence of tortuosity from its measurement frame of reference.The question of whether and ␣ are related has been explored in many contexts, but because it depends on the structure of the heterogeneous medium, no universal relationship is known. It is expected tha...

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Section: Resultsmentioning

confidence: 99%

Changes in brain cell shape create residual extracellular space volume and explain tortuosity behavior during osmotic challenge

Chen

Nicholson

2000

Proc. Natl. Acad. Sci. U.S.A.

123

115

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“…In response to stimulation by light from a dark-adapted state, a transient, localized surge in extracellular Ca 2ϩ has been observed; however, some uncertainty remains concerning the precise initial and final concentrations since the extracellular calcium levels ([Ca 2ϩ ] o ) can depend on pigmentation, the animal model used, and the depth of penetration of the subretinal space by the ion-selective electrode (47)(48)(49) in addition to modulation of the subretinal space volume by other factors (50). For the present analysis, a resting value of [Ca 2ϩ ] o is taken as ϳ1.5 mM, in the middle of the typical tissue [Ca 2ϩ ] o ranging from 1 to 2 mM.…”

Section: Discussionmentioning

confidence: 99%

The N1317H Substitution Associated with Leber Congenital Amaurosis Results in Impaired Interdomain Packing in Human CRB1 Epidermal Growth Factor-like (EGF) Domains

Davis¹,

Handford

Redfield

2007

Journal of Biological Chemistry

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The calcium-binding epidermal growth factor-like (cbEGF) domain is a widely occurring module in proteins of diverse function. Amino acid substitutions that disrupt its structure or calcium affinity have been associated with various disorders. The extracellular portion of CRB1, the human homologue of Drosophila Crumbs, exhibits a modular domain organization that includes EGF and cbEGF domains. The N1317H substitution in the 19th cbEGF domain of CRB1 is associated with the serious visual disorder Leber congenital amaurosis. We have investigated the structure and Ca 2؉ binding of recombinant wild-type and N1317H CRB1 fragments (EGF18-cbEGF19) using NMR and find that Ca 2؉ binding is altered, resulting in disruption of long range interactions between adjacent EGF domains in CRB1. From these observations, we propose that this substitution affects the structural integrity of CRB1 in the inter-photoreceptor matrix of the retina, where it is expressed. Furthermore, we identify disease-causing substitutions in other cbEGF-containing proteins that are likely to result in similar disruption of interdomain packing, supporting the hypothesis that the tandem cbEGF domain linkages are critical for the structure and function of proteins containing cbEGF domains.CRB1 is the human homologue of Drosophila Crumbs, a well conserved gene with homologues across multiple phyla (1). In Drosophila, the Crumbs protein is expressed in all ectodermally derived epithelial cells, which includes photoreceptors, and its disruption results in a discontinuous cuticle and extensive cell death (2, 3). In higher organisms, the orthologues CRB2 and CRB3 have a similarly broad expression profile (4, 5), but CRB1 is restricted to brain and retina (6). The expression of CRB1 in retina has been localized to the subapical region adjacent to the outer limiting membrane, a region analogous to the zonula adherens in Drosophila where a similar localization of the protein is observed (7-9).Unsurprisingly from its localization in humans, mutations in CRB1 have been associated with a number of visual disorders including retinitis pigmentosa with (10, 11) or without (11, 12) preserved para-arteriolar retinal pigment epithelium, paravenous pigmented chorioretinal atrophy (13), and Leber congenital amaurosis (LCA) 3 (14, 15). Of these disorders, LCA is the most severe form of inherited retinal dystrophy and is characterized by severe visual impairment from birth or very early life and a decreased or absent electroretinogram response (16). LCA is generally inherited in an autosomal recessive manner (16). Mutations in CRB1 represent a significant cause (10 -13%) of LCA among the identified LCA loci; missense, nonsense, and splice site mutations together with insertions and deletions have been identified (17, 18). The majority of disease-associated missense mutations in CRB1 have been localized to the extracellular region of the protein, and substitutions associated with the various disorders are approximately evenly distributed along its length, with no unambiguous g...

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“…Crewther (6) hypothesized, on the basis of acute in vivo and in vitro electrophysiological studies in retina under constant illumination (7)(8)(9)(10), that reduced luminance modulation under an occluder would lead to a reaccumulation of potassium in the subretinal space (SRS), volume changes in the SRS (8,11), and a reduction in associated fluid outflow across the retinal pigment epithelium (RPE) (12).…”

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confidence: 99%

Ionic control of ocular growth and refractive change

Liang

Junghans

Crewther

2006

Proc. Natl. Acad. Sci. U.S.A.

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The physiological mechanisms underlying the abnormal vitreal and ocular growth and myopic refractive errors induced under conditions of visual form deprivation in many animal species, including humans, are unknown. This study demonstrates, using energy dispersive x-ray microanalysis, a systematic pattern of changes in the elemental distribution of K, Na, and Cl across the entire retina in experimental form deprivation myopia and in the 5 days required for refractive normalization after occluder removal. In our report we link the ionic environment associated with physiological activity of the retina under a translucent occluder to refractive change and describe large but reversible environmentally driven increases in potassium, sodium, and chloride abundances in the neural retina. Our results are consistent with the notion of ionically driven fluid movements as the vector underlying the myopic increase in ocular size. New treatments for myopia, which currently affects nearly half of the human population, may result.form deprivation myopia ͉ retinal pigment epithelium ͉ x-ray microanalysis

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Light-induced changes of extracellular ions and volume in the isolated chick retina–pigment epithelium preparation

Cited by 67 publications

References 37 publications

Changes in brain cell shape create residual extracellular space volume and explain tortuosity behavior during osmotic challenge

Changes in brain cell shape create residual extracellular space volume and explain tortuosity behavior during osmotic challenge

The N1317H Substitution Associated with Leber Congenital Amaurosis Results in Impaired Interdomain Packing in Human CRB1 Epidermal Growth Factor-like (EGF) Domains

Ionic control of ocular growth and refractive change

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