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Establishment of A Mouse Model of Aqueous Deficiency Dry Eye
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Dry eye: a protein conformational disease.

Mohammad Azharuddin1, Jayesh Khandelwal2, Himadri Datta2

  • 1Department of Biochemistry and Centre for Excellence in Biomedical Engineering and Systems Biology, University of Calcutta, Ballygunge Campus, Kolkata, India.

Investigative Ophthalmology & Visual Science
|February 5, 2015
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Summary

Aqueous-deficient dry eyes (ADDE) may be a protein conformational disease. Studies show increased protein aggregation and oxidative stress in ADDE patients, suggesting new diagnostic and therapeutic strategies.

Keywords:
conformational diseasedry eyedynamic light scatteringprotein aggregation

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Area of Science:

  • Ophthalmology
  • Biochemistry
  • Protein Science

Background:

  • Aqueous-deficient dry eyes (ADDE) management currently relies on empirical treatments.
  • Understanding the underlying molecular mechanisms of ADDE is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate if aqueous-deficient dry eyes (ADDE) is a protein conformational disease.
  • To explore potential new theranostic approaches for ADDE based on protein structure.

Main Methods:

  • Recruited 50 ADDE patients and 46 healthy controls.
  • Performed standard dry eye tests (Schirmer's, tear breakup time, etc.).
  • Analyzed tear proteins using dynamic light scattering (DLS), FPLC, and synchronous fluorescence spectroscopy (SFS) to assess protein aggregation and oxidative stress.

Main Results:

  • ADDE patients exhibited significantly higher levels of aggregated tear proteins compared to controls.
  • Tear proteins in ADDE patients showed larger aggregate sizes (up to 300 nm) than in controls (<50 nm).
  • Synchronous fluorescence spectroscopy indicated increased oxidative stress in ADDE patients, correlating with protein aggregation.

Conclusions:

  • Aqueous-deficient dry eyes (ADDE) is likely a protein conformational disease.
  • Unlike other conformational diseases, ADDE may involve structural changes across a significant portion of the tear proteome.
  • Findings suggest a shift from empirical treatment to targeted theranostics for ADDE.