Evidence of corneal lymphangiogenesis in dry eye disease: A potential link to adaptive immunity?

Sunali Goyal, Sunil K. Chauhan, Jaafar El-Annan, Nambi Nallasamy, Qiang Zhang, Reza Dana

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Objective: To determine the effect of desiccating stress on corneal angiogenic responses in dry eye disease (DED) using a murine model. Methods: Dry eye was induced in murine eyes using high-flow desiccated air. Corneas were double stained with CD31 (panendothelial marker) and LYVE-1 (lymphatic endothelial marker). Real-time polymerase chain reaction was performed to quantify expression of vascular endothelial growth factors (VEGF-A, VEGF-C, and VEGF-D) and their receptors (VEGFR-2 and VEGFR-3) in the cornea on days 6, 10, and 14. Enumeration of CD11b+/LYVE-1+ monocytic cells was performed in corneas with DED on day 14. Flow cytometric evaluation of the draining lymph nodes in normal mice and mice with DED was performed to determine whether DED is associated with homing of mature (major histocompatibility complex class IIhi) antigen-presenting cells to the lymphoid compartment. Results: Lymphatic vessels unaccompanied by blood vessels were seen growing toward the center of corneas with DED. Significant increases in lymphatic area (P<.001) and lymphatic caliber (P<.02) were seen on day 14 of disease. Lymphangiogenic-specific VEGF-D and VEGFR-3 levels increased earliest on day 6 followed by increased VEGF-C, VEGF-A, and VEGFR-2 levels. Increased recruitment of CD11b+/LYVE-1+ monocytic cells to the cornea and homing of mature CD11b+ antigen-presenting cells to the draining lymph nodes were also associated with DED. Conclusion: Low-grade inflammation associated with DED is an inducer of lymphangiogenesis without accompanying hemangiogenesis.

Original languageEnglish (US)
Pages (from-to)819-824
Number of pages6
JournalArchives of Ophthalmology
Volume128
Issue number7
DOIs
StatePublished - Jul 2010
Externally publishedYes

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Lymphangiogenesis
Eye Diseases
Adaptive Immunity
Cornea
Vascular Endothelial Growth Factor D
Vascular Endothelial Growth Factor Receptor-3
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factor Receptor-2
Antigen-Presenting Cells
Vascular Endothelial Growth Factor A
CD11b Antigens
Vascular Endothelial Growth Factors
Lymph Nodes
Lymphatic Vessels
Major Histocompatibility Complex
Blood Vessels
Real-Time Polymerase Chain Reaction
Air
Inflammation

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Evidence of corneal lymphangiogenesis in dry eye disease : A potential link to adaptive immunity? / Goyal, Sunali; Chauhan, Sunil K.; El-Annan, Jaafar; Nallasamy, Nambi; Zhang, Qiang; Dana, Reza.

In: Archives of Ophthalmology, Vol. 128, No. 7, 07.2010, p. 819-824.

Research output: Contribution to journalArticle

Goyal, Sunali ; Chauhan, Sunil K. ; El-Annan, Jaafar ; Nallasamy, Nambi ; Zhang, Qiang ; Dana, Reza. / Evidence of corneal lymphangiogenesis in dry eye disease : A potential link to adaptive immunity?. In: Archives of Ophthalmology. 2010 ; Vol. 128, No. 7. pp. 819-824.
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title = "Evidence of corneal lymphangiogenesis in dry eye disease: A potential link to adaptive immunity?",
abstract = "Objective: To determine the effect of desiccating stress on corneal angiogenic responses in dry eye disease (DED) using a murine model. Methods: Dry eye was induced in murine eyes using high-flow desiccated air. Corneas were double stained with CD31 (panendothelial marker) and LYVE-1 (lymphatic endothelial marker). Real-time polymerase chain reaction was performed to quantify expression of vascular endothelial growth factors (VEGF-A, VEGF-C, and VEGF-D) and their receptors (VEGFR-2 and VEGFR-3) in the cornea on days 6, 10, and 14. Enumeration of CD11b+/LYVE-1+ monocytic cells was performed in corneas with DED on day 14. Flow cytometric evaluation of the draining lymph nodes in normal mice and mice with DED was performed to determine whether DED is associated with homing of mature (major histocompatibility complex class IIhi) antigen-presenting cells to the lymphoid compartment. Results: Lymphatic vessels unaccompanied by blood vessels were seen growing toward the center of corneas with DED. Significant increases in lymphatic area (P<.001) and lymphatic caliber (P<.02) were seen on day 14 of disease. Lymphangiogenic-specific VEGF-D and VEGFR-3 levels increased earliest on day 6 followed by increased VEGF-C, VEGF-A, and VEGFR-2 levels. Increased recruitment of CD11b+/LYVE-1+ monocytic cells to the cornea and homing of mature CD11b+ antigen-presenting cells to the draining lymph nodes were also associated with DED. Conclusion: Low-grade inflammation associated with DED is an inducer of lymphangiogenesis without accompanying hemangiogenesis.",
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AU - Chauhan, Sunil K.

AU - El-Annan, Jaafar

AU - Nallasamy, Nambi

AU - Zhang, Qiang

AU - Dana, Reza

PY - 2010/7

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N2 - Objective: To determine the effect of desiccating stress on corneal angiogenic responses in dry eye disease (DED) using a murine model. Methods: Dry eye was induced in murine eyes using high-flow desiccated air. Corneas were double stained with CD31 (panendothelial marker) and LYVE-1 (lymphatic endothelial marker). Real-time polymerase chain reaction was performed to quantify expression of vascular endothelial growth factors (VEGF-A, VEGF-C, and VEGF-D) and their receptors (VEGFR-2 and VEGFR-3) in the cornea on days 6, 10, and 14. Enumeration of CD11b+/LYVE-1+ monocytic cells was performed in corneas with DED on day 14. Flow cytometric evaluation of the draining lymph nodes in normal mice and mice with DED was performed to determine whether DED is associated with homing of mature (major histocompatibility complex class IIhi) antigen-presenting cells to the lymphoid compartment. Results: Lymphatic vessels unaccompanied by blood vessels were seen growing toward the center of corneas with DED. Significant increases in lymphatic area (P<.001) and lymphatic caliber (P<.02) were seen on day 14 of disease. Lymphangiogenic-specific VEGF-D and VEGFR-3 levels increased earliest on day 6 followed by increased VEGF-C, VEGF-A, and VEGFR-2 levels. Increased recruitment of CD11b+/LYVE-1+ monocytic cells to the cornea and homing of mature CD11b+ antigen-presenting cells to the draining lymph nodes were also associated with DED. Conclusion: Low-grade inflammation associated with DED is an inducer of lymphangiogenesis without accompanying hemangiogenesis.

AB - Objective: To determine the effect of desiccating stress on corneal angiogenic responses in dry eye disease (DED) using a murine model. Methods: Dry eye was induced in murine eyes using high-flow desiccated air. Corneas were double stained with CD31 (panendothelial marker) and LYVE-1 (lymphatic endothelial marker). Real-time polymerase chain reaction was performed to quantify expression of vascular endothelial growth factors (VEGF-A, VEGF-C, and VEGF-D) and their receptors (VEGFR-2 and VEGFR-3) in the cornea on days 6, 10, and 14. Enumeration of CD11b+/LYVE-1+ monocytic cells was performed in corneas with DED on day 14. Flow cytometric evaluation of the draining lymph nodes in normal mice and mice with DED was performed to determine whether DED is associated with homing of mature (major histocompatibility complex class IIhi) antigen-presenting cells to the lymphoid compartment. Results: Lymphatic vessels unaccompanied by blood vessels were seen growing toward the center of corneas with DED. Significant increases in lymphatic area (P<.001) and lymphatic caliber (P<.02) were seen on day 14 of disease. Lymphangiogenic-specific VEGF-D and VEGFR-3 levels increased earliest on day 6 followed by increased VEGF-C, VEGF-A, and VEGFR-2 levels. Increased recruitment of CD11b+/LYVE-1+ monocytic cells to the cornea and homing of mature CD11b+ antigen-presenting cells to the draining lymph nodes were also associated with DED. Conclusion: Low-grade inflammation associated with DED is an inducer of lymphangiogenesis without accompanying hemangiogenesis.

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