Expressions of Specialized Collagens in the Cornea

Project Details

Description

The cornea uses extracellular matrix (ECM) molecules, in particular, collagens, to set up an
architecture that serves two crucial functions: refraction and transmission of light. Our overall objective is to
understand how the cornea regulates the synthesis, assembly, and differential expression of a specific set of
collagens to achieve this architecture. Collagen fibrils in the corneal stroma are thin, uniform diameter
structures, evenly spaced apart at discreet distances, and arranged in orthogonal layers. We hypothesize
that fibrillar collagen XXIV and FACIT collagen XIV contribute to regulating the fibril diameters, and that
FACIT collagen XII regulates the spacing of the fibrils in the corneal stroma.
To address these hypotheses we propose in Aim 1 to determine what changes occur in the cornea of
a transgenic mouse that secretes reduced quantites of type XII collagen. Our preliminary data indicate that
collagen fibrils are spaced much closer together in the transgenic cornea. The fibril diameters, fibril spacing
and biomechanical strength of transgenic mouse corneas will be measured and compared to wild type mice.
We will also assess how other matrix molecules are affected by a paucity of collagen XII and what are the
ophthalmologic consquences of making a cornea with reduced levels of collagen XII. It is possible that these
mice represent an animal model for the human corneal disease, keratoconus. In Aim 2, we will determine
whether collagen XII is a proteoglycan in the cornea, as well as a collagen, similar to its structure in cartilage.
This is of interest in the cornea because proteoglycans have been implicated in correct collagen fibril
spacing, and mice with the known corneal proteoglycan genes knocked out have not shown significant
alterations in corneal fibril spacing. If collagen XII is a proteoglycan, we will measure what percentage of the
total proteoglycan it represents. In Aim 3 we will demonstrate whether newly identified fibrillar collagen type
XXIV and FACIT collagen XIV are fibril diameter regulators in the developing chick cornea. The amount of
collagen XXIV and XIV secreted in the cornea will be reduced by injecting into the cornea in ovo virus
encoding truncated versions of each collagen. Truncated and normal chains will combine and be degraded
intracellularly, reducing the amount of secreted collagen XIV and XXIV. The alterations in fibril architecture
resulting from the dominant negative phenotype will be evaluated by transmission electron microscopy.
StatusFinished
Effective start/end date5/1/9111/30/12

Funding

  • National Eye Institute: $339,608.00
  • National Eye Institute
  • National Eye Institute: $339,608.00
  • National Eye Institute
  • National Eye Institute: $378,483.00
  • National Eye Institute
  • National Eye Institute: $339,608.00
  • National Eye Institute: $443,425.00
  • National Eye Institute: $77,750.00
  • National Eye Institute: $469,538.00
  • National Eye Institute
  • National Eye Institute: $203,953.00
  • National Eye Institute
  • National Eye Institute
  • National Eye Institute
  • National Eye Institute
  • National Eye Institute: $438,584.00
  • National Eye Institute: $477,898.00
  • National Eye Institute: $269,373.00
  • National Eye Institute
  • National Eye Institute: $447,590.00
  • National Eye Institute

ASJC

  • Genetics
  • Ophthalmology

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