Human nuclear age-related cataract is the most common type of cataract requiring corrective surgery in North America and remains a leading cause of blindness throughout the world. In this competing continuation application the main goal is to identify and characterize the precise cellular changes that produce scattering centers within human nuclei. Significant progress has been made in recent years in characterizing the alterations to fiber cells that may produce increased light scattering within human lens nuclei, as well as to an understanding the nature of aging, compaction and intercellular communication in the normal human lenses. The proposed research will build on the previous successes using morphological approaches and will employ a variety of modern electron microscopy techniques including scanning and transmission electron microscopy, cryo microscopy, 3D tomography, Fourier analysis, fluorescent and brightfield light microscopy and laser scanning and two-photon confocal microscopy. We propose to document the molecular organization of the cytoplasm and the distribution of specialized junctions in normal lenses. Emphasis will be given to junctions containing MEP/Aquaporin0 which have been hypothesized to provide a pathway for water transport and serve as adhering junctions. Membranes isolated from different regions of human lenses will be examined to determine the molecular organization using fluorescent and gold particle labeling and to characterize the adhesive junctions. Changes in the junctions and within the cytoplasm of fiber cells during nuclear cataract formation will be documented, especially the multilamellar bodies we described recently as potential scattering centers. We expect that this work will contribute to a better understanding of the current hypotheses of cataract formation and to strategies that could slow or prevent the progression of cataracts in the elderly.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY008148-14
Application #
6736844
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Liberman, Ellen S
Project Start
1988-09-01
Project End
2007-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
14
Fiscal Year
2004
Total Cost
$290,027
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Bassnett, Steven; Costello, M Joseph (2017) The cause and consequence of fiber cell compaction in the vertebrate lens. Exp Eye Res 156:50-57
Costello, M Joseph; Brennan, Lisa A; Mohamed, Ashik et al. (2016) Identification and Ultrastructural Characterization of a Novel Nuclear Degradation Complex in Differentiating Lens Fiber Cells. PLoS One 11:e0160785
Mohamed, Ashik; Gilliland, Kurt O; Metlapally, Sangeetha et al. (2013) Simple fixation and storage protocol for preserving the internal structure of intact human donor lenses and extracted human nuclear cataract specimens. Mol Vis 19:2352-9
Costello, M Joseph; Mohamed, Ashik; Gilliland, Kurt O et al. (2013) Ultrastructural analysis of the human lens fiber cell remodeling zone and the initiation of cellular compaction. Exp Eye Res 116:411-8
Costello, M Joseph; Brennan, Lisa A; Basu, Subharsee et al. (2013) Autophagy and mitophagy participate in ocular lens organelle degradation. Exp Eye Res 116:141-50
Costello, M Joseph; Burette, Alain; Weber, Mariko et al. (2012) Electron tomography of fiber cell cytoplasm and dense cores of multilamellar bodies from human age-related nuclear cataracts. Exp Eye Res 101:72-81
Costello, M Joseph; Johnsen, Sonke; Metlapally, Sangeetha et al. (2010) Multilamellar spherical particles as potential sources of excessive light scattering in human age-related nuclear cataracts. Exp Eye Res 91:881-9
Costello, M J; Johnsen, Sonke; Metlapally, Sangeetha et al. (2008) Ultrastructural analysis of damage to nuclear fiber cell membranes in advanced age-related cataracts from India. Exp Eye Res 87:147-58
Metlapally, S; Costello, M J; Gilliland, K O et al. (2008) Analysis of nuclear fiber cell cytoplasmic texture in advanced cataractous lenses from Indian subjects using Debye-Bueche theory. Exp Eye Res 86:434-44
Costello, M Joseph (2006) Cryo-electron microscopy of biological samples. Ultrastruct Pathol 30:361-71