The pulling, pushing and fusing of lens fibers

Rao, Ponugoti Vasantha

doi:10.4161/cam.2.3.6495

Cited by 10 publications

(10 citation statements)

References 44 publications

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“…During differentiation, newly forming fiber cells elongate bidirectionally and move deeper into the lens as their basal ends migrate along the posterior capsule and their apical ends migrate along the apical surface of the anterior lens epithelium (Kuszak et al, 2004; Rao, 2008). Endoplasmic reticulum and nuclei are present in the newly forming fiber cells; however as fiber cells mature, they undergo denucleation and degrade their cytoplasmic organelles as a feature of terminal differentiation.…”

Section: Resultsmentioning

confidence: 99%

Unfolded Protein Response (UPR) is activated during normal lens development

Firtina

Duncan

2011

Gene Expression Patterns

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The lens of the eye is a transparent structure responsible for focusing light onto the retina. It is composed of two morphologically different cell types, epithelial cells found on the anterior surface and the fiber cells that are continuously formed by the differentiation of epithelial cells at the lens equator. The differentiation of an epithelial precursor cell into a fiber cell is associated with a dramatic increase in membrane protein synthesis. How the terminally differentiating fiber cells cope with the increased demand on the endoplasmic reticulum for this membrane protein synthesis is not known. In the present study, we have found evidence of Unfolded Protein Response (UPR) activation during normal lens development and differentiation in the mouse. The ER-resident chaperones, immunoglobulin heavy chain binding protein (BiP) and protein disulfide isomerase (PDI), were expressed at high levels in the newly forming fiber cells of embryonic lenses. These fiber cells also expressed the UPR-associated molecules; XBP1, ATF6, phospho-PERK and ATF4 during embryogenesis. Moreover, spliced XBP1, cleaved ATF6, and phospho-eIF2 were detected in embryonic mouse lenses suggesting that UPR pathways are active in this tissue. These results propose a role for UPR activation in lens fiber cell differentiation during embryogenesis.

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Section: Resultsmentioning

confidence: 99%

Unfolded Protein Response (UPR) is activated during normal lens development

Firtina

Duncan

2011

Gene Expression Patterns

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“…Small GTPases are the major modulators of the actin cytoskeleton (Burridge and Wennerberg, 2004; Cullen, 2006; Rao, 2008). As molecular switches, Rho GTPases exist in two states: an inactive state bound to GDP and an active state in which GDP is replaced by GTP.…”

Section: Introductionmentioning

confidence: 99%

Traumatic Noise Activates Rho-Family GTPases through Transient Cellular Energy Depletion

et al. 2012

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Small GTPases mediate transmembrane signaling and regulate the actin cytoskeleton in eukaryotic cells. Here, we characterize the auditory pathology of adult male CBA/J mice exposed to traumatic noise (2–20 kHz; 106 dB; 2 h). Loss of outer hair cells was evident 1 h after noise exposure in the basal region of the cochlea and spread apically with time, leading to permanent threshold shifts of 35, 60, and 65 dB at 8, 16, and 32 kHz. Several biochemical and molecular changes correlated temporally with the loss of cells. Immediately after exposure, the concentration of ATP decreased in cochlear tissue and reached a minimum after 1 h while the immunofluorescent signal for p-AMPKα significantly increased in sensory hair cells at that time. Levels of active Rac1 increased, whereas those of active RhoA decreased significantly 1 h after noise attaining a plateau at 1 to 3 h; the formation of a RhoA-p140mDia complex was consistent with an activation of Rho GTPase pathways. Also at 1 to 3 h after exposure, the caspase-independent cell death marker, endonuclease G, translocated to the nuclei of outer hair cells. Finally, experiments with the inner ear HEI-OC1 cell line demonstrated that the energy-depleting agent oligomycin enhanced both Rac1 activity and cell death. The sum of the results suggests that traumatic noise induces transient cellular ATP depletion and activates Rho GTPase pathways, leading to death of outer hair cells in the cochlea.

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“…68 In a manner similar to Rho GTPases, ILK has a pivotal role in regulating actin cytoskeletal dynamics and cell adhesive interactions, 72 events presumed to enable migration of the fibers along the anterior epithelium. 75 Studies of ILK deletion in vascular smooth muscle cells suggest that ILK regulates cell contractility and myosin light chain phosphorylation via the Rho pathway. 76 A potential mechanism that remains to be explored is whether ILK could regulate apical-apical adhesion through a Rho-family dependent mechanism.…”

Section: Is Ilk Required For Apical-apical Cell Interaction?mentioning

confidence: 99%

Integrin-Linked Kinase Deletion in the Developing Lens Leads to Capsule Rupture, Impaired Fiber Migration and Non-Apoptotic Epithelial Cell Death

Cammas

Wolfe

Choi

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The lens is a powerful model system to study integrinmediated cell-matrix interaction in an in vivo context, as it is surrounded by a true basement membrane, the lens capsule. To characterize better the function of integrin-linked kinase (ILK), we examined the phenotypic consequences of its deletion in the developing mouse lens.METHODS. ILK was deleted from the embryonic lens either at the time of placode invagination using the Le-Cre line or after initial lens formation using the Nestin-Cre line.RESULTS. Early deletion of ILK leads to defects in extracellular matrix deposition that result in lens capsule rupture at the lens vesicle stage (E13.5). If ILK was deleted at a later time-point after initial establishment of the lens capsule, rupture was prevented. Instead, ILK deletion resulted in secondary fiber migration defects and, most notably, in cell death of the anterior epithelium (E18.5 -P0). Remarkably, dying cells did not stain positively for terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) or activated-caspase 3, suggesting that they were dying from a non-apoptotic mechanism. Moreover, cross to a Bax fl/fl /Bak -/-mouse line that is resistant to most forms of apoptosis failed to promote cell survival in the ILKdeleted lens epithelium. Electron microscopy revealed the presence of numerous membranous vacuoles containing degrading cellular material.CONCLUSIONS. Our study reveals a role for ILK in extracellular matrix organization, fiber migration, and cell survival. Furthermore, to our knowledge we show for the first time that ILK disruption results in non-apoptotic cell death in vivo. (Invest Ophthalmol Vis Sci. 2012;53:3067-3081)

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The pulling, pushing and fusing of lens fibers

Cited by 10 publications

References 44 publications

Unfolded Protein Response (UPR) is activated during normal lens development

Unfolded Protein Response (UPR) is activated during normal lens development

Traumatic Noise Activates Rho-Family GTPases through Transient Cellular Energy Depletion

Integrin-Linked Kinase Deletion in the Developing Lens Leads to Capsule Rupture, Impaired Fiber Migration and Non-Apoptotic Epithelial Cell Death

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