Differentiation of transparency in a lens cell involves a series of stages in which organelles disappear, membranes and metabolism become specialized and cytoplasmic proteins are concentrated into a homogeneous, transparent single phase. The results of the previous studies indicate that opacification may occur in stages that resemble the reversal of normal lens cell differentiation. The homogeneous cellular structure becomes disorganized and the cytoplasm is converted from a single transparent phase into two separate phases as light scattering increases. The transition from transparency to opacity is a continuous process which may include an early precataractous stage that is present prior to the observation of obvious light scattering in vivo. Based on the findings of the past project period, I propose the hypothesis that cataract formation includes an early stage in which abnormal molecular interactions initiate subtle structural lens cell opacification. The hypothesis will be tested through the following aims:
Aim I : Characterization of the Early Stages of Opacification.
Aim II : Quantification of Molecular Interactions in Lens Cytoplasm During Early Stages of Cataract Formation.
Aim III : Characterization of Oscillations in Lens Growth During Development of Cataract. The results of these studies are expected to provide an animal model for the early stages of human cataract formation when the opportunity for non-surgical prevention of opacification is greatest.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY004542-12
Application #
3258958
Study Section
Special Emphasis Panel (ZRG1-VISB (01))
Project Start
1982-06-01
Project End
1998-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
12
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Clark, John I (2016) Functional sequences in human alphaB crystallin. Biochim Biophys Acta 1860:240-5
Anderson, David M G; Floyd, Kyle A; Barnes, Stephen et al. (2015) A method to prevent protein delocalization in imaging mass spectrometry of non-adherent tissues: application to small vertebrate lens imaging. Anal Bioanal Chem 407:2311-20
Clark, John I (2013) Self-assembly of protein aggregates in ageing disorders: the lens and cataract model. Philos Trans R Soc Lond B Biol Sci 368:20120104
Gokhin, David S; Nowak, Roberta B; Kim, Nancy E et al. (2012) Tmod1 and CP49 synergize to control the fiber cell geometry, transparency, and mechanical stiffness of the mouse lens. PLoS One 7:e48734
Clark, Tyler J W; Houck, Scott A; Clark, John I (2012) Hemoglobin interactions with ?B crystallin: a direct test of sensitivity to protein instability. PLoS One 7:e40486
Greiling, Teri M S; Clark, John I (2012) New insights into the mechanism of lens development using zebra fish. Int Rev Cell Mol Biol 296:1-61
Qu, Bo; Landsbury, Andrew; Schönthaler, Helia Berrit et al. (2012) Evolution of the vertebrate beaded filament protein, Bfsp2; comparing the in vitro assembly properties of a ""tailed"" zebrafish Bfsp2 to its ""tailless"" human orthologue. Exp Eye Res 94:192-202
Houck, Scott A; Landsbury, Andrew; Clark, John I et al. (2011) Multiple sites in ?B-crystallin modulate its interactions with desmin filaments assembled in vitro. PLoS One 6:e25859
Houck, Scott A; Clark, John I (2010) Dynamic subunit exchange and the regulation of microtubule assembly by the stress response protein human alphaB crystallin. PLoS One 5:e11795
Greiling, Teri M S; Aose, Masamoto; Clark, John I (2010) Cell fate and differentiation of the developing ocular lens. Invest Ophthalmol Vis Sci 51:1540-6

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