The complexity of animal model generation for complex diseases

Peter A. Campochiaro, Daniel Albert, Aneesh Neekhra, Shoujian Wang, Soesiawati R. Darjatmoko, Christine M. Sorenson, Richard R. Dubielzig, Nader Sheibani

Research output: Contribution to journalComment/debate

1 Citation (Scopus)

Abstract

Objectives: To study the progressive changes of intense cyclic light-induced retinal degeneration and to determine whether it results in choroidal neovascularization (CNV). Methods: Albino rats were exposed to 12 hours of 3000-lux cyclic light for 1, 3, or 6 months. Fundus examination, fundus photography, fluorescein and indocyanine green angiography, and optical coherence tomography were performed prior to euthanization. Light-exposed animals were euthanized after 1, 3, or 6 months for histopathological evaluation. Retinas were examined for the presence of 4-hydroxy-2-nonenal- and nitrotyrosine-modified proteins by immunofluorescence staining. Results: Long-term intense cyclic light exposure resulted in retinal degeneration with loss of the outer segments of photoreceptors and approximately two-thirds of the outer nuclear layer as well as development of subretinal pigment epithelium neovascularization after 1 month. Almost the entire outer nuclear layer was absent with the presence of CNV, which penetrated the Bruch membrane and extended into the outer retina after 3 months. Absence of the outer nuclear layer, multiple foci of CNV, retinal pigment epithelial fibrous metaplasia, and connective tissue bands containing blood vessels extending into the retina were observed after 6 months. All intense light-exposed animals showed an increased presence of 4-hydroxy-2-nonenal and nitrotyrosine staining. Optical coherence tomographic and angiographic studies confirmed retinal thinning and leakiness of the newly formed blood vessels. Conclusions: Our results suggest that albino rats develop progressive stages of retinal degeneration and CNV after long-term intense cyclic light exposure, allowing the detailed study of the pathogenesis and treatment of age-related macular degeneration. Clinical Relevance: The ability to study the progressive pathogenesis of age-related macular degeneration and CNV will provide detailed knowledge about the disease and aid in the development of target-specific therapy.

Original languageEnglish (US)
Pages (from-to)657-658
Number of pages2
JournalJAMA - Journal of the American Medical Association
Volume303
Issue number7
DOIs
StatePublished - Feb 17 2010
Externally publishedYes

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Choroidal Neovascularization
Animal Models
Light
Retinal Degeneration
Retina
Macular Degeneration
Blood Vessels
Retinal Neovascularization
Bruch Membrane
Staining and Labeling
Indocyanine Green
Retinal Pigments
Photography
Optical Coherence Tomography
Metaplasia
Fluorescein
Connective Tissue
Fluorescent Antibody Technique
Angiography
Epithelium

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Campochiaro, P. A., Albert, D., Neekhra, A., Wang, S., Darjatmoko, S. R., Sorenson, C. M., ... Sheibani, N. (2010). The complexity of animal model generation for complex diseases. JAMA - Journal of the American Medical Association, 303(7), 657-658. https://doi.org/10.1001/jama.2010.142

The complexity of animal model generation for complex diseases. / Campochiaro, Peter A.; Albert, Daniel; Neekhra, Aneesh; Wang, Shoujian; Darjatmoko, Soesiawati R.; Sorenson, Christine M.; Dubielzig, Richard R.; Sheibani, Nader.

In: JAMA - Journal of the American Medical Association, Vol. 303, No. 7, 17.02.2010, p. 657-658.

Research output: Contribution to journalComment/debate

Campochiaro, PA, Albert, D, Neekhra, A, Wang, S, Darjatmoko, SR, Sorenson, CM, Dubielzig, RR & Sheibani, N 2010, 'The complexity of animal model generation for complex diseases', JAMA - Journal of the American Medical Association, vol. 303, no. 7, pp. 657-658. https://doi.org/10.1001/jama.2010.142
Campochiaro, Peter A. ; Albert, Daniel ; Neekhra, Aneesh ; Wang, Shoujian ; Darjatmoko, Soesiawati R. ; Sorenson, Christine M. ; Dubielzig, Richard R. ; Sheibani, Nader. / The complexity of animal model generation for complex diseases. In: JAMA - Journal of the American Medical Association. 2010 ; Vol. 303, No. 7. pp. 657-658.
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abstract = "Objectives: To study the progressive changes of intense cyclic light-induced retinal degeneration and to determine whether it results in choroidal neovascularization (CNV). Methods: Albino rats were exposed to 12 hours of 3000-lux cyclic light for 1, 3, or 6 months. Fundus examination, fundus photography, fluorescein and indocyanine green angiography, and optical coherence tomography were performed prior to euthanization. Light-exposed animals were euthanized after 1, 3, or 6 months for histopathological evaluation. Retinas were examined for the presence of 4-hydroxy-2-nonenal- and nitrotyrosine-modified proteins by immunofluorescence staining. Results: Long-term intense cyclic light exposure resulted in retinal degeneration with loss of the outer segments of photoreceptors and approximately two-thirds of the outer nuclear layer as well as development of subretinal pigment epithelium neovascularization after 1 month. Almost the entire outer nuclear layer was absent with the presence of CNV, which penetrated the Bruch membrane and extended into the outer retina after 3 months. Absence of the outer nuclear layer, multiple foci of CNV, retinal pigment epithelial fibrous metaplasia, and connective tissue bands containing blood vessels extending into the retina were observed after 6 months. All intense light-exposed animals showed an increased presence of 4-hydroxy-2-nonenal and nitrotyrosine staining. Optical coherence tomographic and angiographic studies confirmed retinal thinning and leakiness of the newly formed blood vessels. Conclusions: Our results suggest that albino rats develop progressive stages of retinal degeneration and CNV after long-term intense cyclic light exposure, allowing the detailed study of the pathogenesis and treatment of age-related macular degeneration. Clinical Relevance: The ability to study the progressive pathogenesis of age-related macular degeneration and CNV will provide detailed knowledge about the disease and aid in the development of target-specific therapy.",
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AU - Albert, Daniel

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AU - Sorenson, Christine M.

AU - Dubielzig, Richard R.

AU - Sheibani, Nader

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AB - Objectives: To study the progressive changes of intense cyclic light-induced retinal degeneration and to determine whether it results in choroidal neovascularization (CNV). Methods: Albino rats were exposed to 12 hours of 3000-lux cyclic light for 1, 3, or 6 months. Fundus examination, fundus photography, fluorescein and indocyanine green angiography, and optical coherence tomography were performed prior to euthanization. Light-exposed animals were euthanized after 1, 3, or 6 months for histopathological evaluation. Retinas were examined for the presence of 4-hydroxy-2-nonenal- and nitrotyrosine-modified proteins by immunofluorescence staining. Results: Long-term intense cyclic light exposure resulted in retinal degeneration with loss of the outer segments of photoreceptors and approximately two-thirds of the outer nuclear layer as well as development of subretinal pigment epithelium neovascularization after 1 month. Almost the entire outer nuclear layer was absent with the presence of CNV, which penetrated the Bruch membrane and extended into the outer retina after 3 months. Absence of the outer nuclear layer, multiple foci of CNV, retinal pigment epithelial fibrous metaplasia, and connective tissue bands containing blood vessels extending into the retina were observed after 6 months. All intense light-exposed animals showed an increased presence of 4-hydroxy-2-nonenal and nitrotyrosine staining. Optical coherence tomographic and angiographic studies confirmed retinal thinning and leakiness of the newly formed blood vessels. Conclusions: Our results suggest that albino rats develop progressive stages of retinal degeneration and CNV after long-term intense cyclic light exposure, allowing the detailed study of the pathogenesis and treatment of age-related macular degeneration. Clinical Relevance: The ability to study the progressive pathogenesis of age-related macular degeneration and CNV will provide detailed knowledge about the disease and aid in the development of target-specific therapy.

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