Tractional Force Generation by Human Müller Cells: Growth Factor Responsiveness and Integrin Receptor Involvement

Guidry, Clyde; Bradley, Kelley M.; King, Jeffery L.

doi:10.1167/iovs.02-0046

Cited by 79 publications

(51 citation statements)

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“…These concentrations were generally consistent with several other studies of diabetic vitreous, reporting IGF-I concentrations of 1.4 (22) (23) and 45 (25) ng/ml. These concentrations translate into vitreous growth factor molarities ranging from 0.15 to 0.89 nmol/l IGF-I and 3.1 to 6.0 nmol/l IGF-II, either of which is sufficient to induce Mü ller cell responses in our assay system (18,19). Thus, our observations of vitreous biological activity attributable to IGF-related species are consistent with reports of growth factor concentrations in diabetic vitreous.…”

Section: Discussionsupporting

confidence: 89%

“…Vitreous concentrations of IGF-I also increase diabetes to mean concentrations ranging from 1.4 to 6.3 ng/ml (21)(22)(23)(24)(25)(26)(27). In contrast to PDGF, these levels are well above the threshold of Mü ller cell sensitivity (18,19), suggesting that IGF-I is present in diabetic vitreous in quantities sufficient to drive Mü ller cell fibrocontractive responses. Although the evidence in support of IGF-I as a vitreal Mü ller cell stimulus is compelling, other observations suggest that this relationship may be more complex.…”

mentioning

confidence: 98%

“…Studies of Mü ller cells isolated from normal human and porcine retina revealed an extraordinary capacity for changes in cell phenotype that include de novo expression of the myoid marker ␣ smooth muscle actin and, with this, the capacity to generate tractional forces (17)(18)(19). Interestingly, Mü ller cell tractional force generation is not constitutive but is stimulated by the presence of certain exogenous growth factors, including members of the platelet-derived growth factor (PDGF) family and IGF-I (18,19).…”

mentioning

confidence: 99%

“…Interestingly, Mü ller cell tractional force generation is not constitutive but is stimulated by the presence of certain exogenous growth factors, including members of the platelet-derived growth factor (PDGF) family and IGF-I (18,19). Although vitreous PDGF reportedly increases in diabetes, the mean reported concentration of 100 pg/ml (20) is below the threshold of Mü ller cell sensitivity (18,19) and seems unlikely to drive tractional force generation. Vitreous concentrations of IGF-I also increase diabetes to mean concentrations ranging from 1.4 to 6.3 ng/ml (21)(22)(23)(24)(25)(26)(27).…”

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confidence: 99%

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Changes in IGF Activities in Human Diabetic Vitreous

et al. 2004

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Mü ller cells, the principal glia of the retina, generate tractional forces in response to IGF-I and plateletderived growth factor and are present in diabetic fibrovascular scar tissues causing traction retinal detachment. While diabetes-associated increases in vitreous IGFs have been reported, paradoxically high concentrations of these same growth factors in normal vitreous suggest the presence of more complex mechanisms regulating growth factor bioavailability. To define diabetes-associated changes in vitreous biological activity, the stimulatory effects of 68 samples were evaluated using Mü ller cell tractional force generation as a target bioassay. Dose-response profiles were used to calculate vitreous specific activity (per unit protein) and total vitreous activity (per unit volume). Vitreous samples from patients lacking diabetes or other retinal pathology had undetectable or low activities, whereas diabetic retinopathy was associated with 6.9-and 8.7-fold increases in vitreous specific and total activities, respectively. Secondary analyses revealed no activity differences associated with patient sex, age, or the presence of vitreous hemorrhage. However, compared with diabetes alone, the presence of proliferative diabetic retinopathy was associated with additional 2.3-fold increases in vitreous specific and total activities. Vitreous dose-response assays performed with and without growth factor-neutralizing antibodies enable attribution of vitreous activity to IGFs (53.9%) and, to a lesser extent, platelet-derived growth factors (14.5%). Because the observed increases in vitreous growth factor activity grossly exceed the reported increases in growth factor concentration, these data indicate that diabetes-associated changes in vitreous biological activity involve more complex biochemical changes that ultimately yield increased growth factor bioavailability and/or Mü ller cell responsiveness. Diabetes 53: 2428 -2435, 2004

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Section: Discussionsupporting

confidence: 89%

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confidence: 98%

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confidence: 99%

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Changes in IGF Activities in Human Diabetic Vitreous

et al. 2004

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“…Integrins are also among various factors that cause retinal detachment in proliferative diabetic retinopathy and proliferative vitreoretinopathy (Kupper and Ferguson 1993;Guidry et al 2003). In rats, blockade of α4 integrin diminished diabetes-induced increase in NF-kappaB activation, VEGF and TNF-alpha levels and significantly reduced leukocyte adhesion and vascular leakage (Iliaki et al 2009).…”

Section: Established Functions Of Integrins In the Eye And Their Assomentioning

confidence: 99%

The integrin needle in the stromal haystack: emerging role in corneal physiology and pathology

Parapuram

Hodge

2014

J. Cell Commun. Signal.

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Several studies have established the role of activated corneal keratocytes in the fibrosis of the cornea. However, the role of keratocytes in maintaining the structural integrity of a normal cornea is less appreciated. We focus on the probable functions of integrins in the eye and of the importance of integrin-mediated keratocyte interactions with stromal matrix in the maintenance of corneal integrity. We point out that further understanding of how keratocytes interact with their matrix could establish a novel direction in preventing corneal pathology including loss of structural integrity as in keratoconus or as in fibrosis of the corneal stroma.Keywords Cornea . Keratocytes . Corneal stroma . Extracellular matrix . Integrins . KeratoconusThe simple cellular organization of the cornea is belied by its fascinating specialization for transparency. The cornea has three main tissue layers, the outer epithelium, the stroma in the middle and the inner endothelial layer. The stromal connective tissue, the layer mainly responsible for the corneal configuration, constituting nearly 80 % of the thickness of the cornea, is extremely resilient, capable of resisting intraocular pressure and protecting the posterior structures of the eye. The stromal tissue consists of lamellae of orthogonally arranged collagen fibrils surrounded by proteoglycans; in between the lamellae of collagen are found the keratocytes. The nearorderly arrangement of collagen lamellae, the narrow diameter of the collagen fibrils, regular interfibrillar space, associated proteoglycans and the expression of crystalline proteins in the keratocytes (Birk 2001;Kao and Liu 2002;Jester et al. 2007; Hassell and Birk 2010) are some of the main factors responsible for corneal transparency. Consequently, the factors affecting corneal transparency such as fibrotic changes due to disease or injury are problems primarily associated with the stroma. Thus it is important to achieve further understanding of the mechanisms by which the stroma acquires and maintains its structural integrity and its transparency.

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Neurosphere cell differentiation to aldynoglia promoted by olfactory ensheathing cell conditioned medium

Doncel‐Pérez

Caballero-Chacón

Nieto–Sampedro

2009

Glia

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Cells from central nervous system with morphology similar to radial glia and properties intermediate between astrocytes and Schwann cells were called growth-promoting glia or aldynoglia. These cells are present in adult brain olfactory bulb, hypothalamus, hypophysis, pineal gland and in the developing brain, and spinal cord (Cameron and Rakic (1991) Glia 4:124-137; Gudiño-Cabrera and Nieto-Sampedro (2000) 30:49-63). We report now that neurosphere cells, abundantly generated from E15 rat or E13 mouse corpus striatum, differentiate to aldynoglia-like cells when plated onto an adhesive substrate, and cultured in the presence of olfactory ensheathing cell conditioned medium, supplemented with EGF and bFGF. The immunophenotype, mRNA expression (microarray and RT-PCR analysis), neurite growth-promoting and ensheathing properties of the cells derived from neurospheres were similar to those of aldynoglia. Neurosphere-derived, aldynoglia-like cells expressed, with respect to neurospheres, very increased levels of GFAP, high levels of nestin and vimentin, extracellular matrix proteins, and inhibitors of the catabolism of those extracellular matrix proteins.

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Tractional Force Generation by Human Müller Cells: Growth Factor Responsiveness and Integrin Receptor Involvement

Cited by 79 publications

References 25 publications

Changes in IGF Activities in Human Diabetic Vitreous

Changes in IGF Activities in Human Diabetic Vitreous

The integrin needle in the stromal haystack: emerging role in corneal physiology and pathology

Neurosphere cell differentiation to aldynoglia promoted by olfactory ensheathing cell conditioned medium

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