・ (Pro) renin receptor^1）and the renin-angiotensin system^2）were discovered to be important pathological factors in the control of the disease condition of conjunctival extranodal marginal zone B-cell lymphoma^3）

・We identified (pro) renin receptor and the renin-angiotensin system as promising molecular targets for drug development.

Conjunctiva is the tissue that covers the surface of the eye, and is the first line of defense against pathogens from the outside. This defense mechanism is an immune mechanism controlled by the conjunctival lymphoid, which activates lymphocyte type B-cells, T-cells, and dendritic cells, when a pathogen is detected. The most frequent tissue type of malignant lymphoma on conjunctiva is extranodal marginal zone B-cell lymphoma, which is observed in 7% of cases of non-Hodgkin’s B-cell lymphoma⁴⁾.

The research team of Professor Susumu Ishida, Specially Appointed Lecturer Atsuhiro Kanda, Graduate Student Erdal Tan Ishizuka, and others of Department of Ophthalmology, Hokkaido University Graduate School of Medicine, clearly identified for the first time that tissue renin-angiotensin system is involved in the fibrosis and metastasis of conjunctival extranodal marginal zone B-cell lymphoma, and (pro) renin receptor which is located upstream is an important key molecule in human tissue. This research achievement is expected to greatly contribute to future drug discovery research, since it clearly identifies the target for new pharmacological therapy. Furthermore, this study was carried out as a part of “The Matching Program for Innovations in Future Drug Discovery and Medical Care” (Hokkaido University) under the Creation of Innovation for Advanced Interdisciplinary Areas Program of Ministry of Education, Culture, Sports, Science and Technology.

Note 1) (Pro) renin receptor: Functions to activate the receptor itself and promote the renin-angiotensin system by binding with prorenin.

Note 2) Renin-angiotensin system (RAS): One of the blood pressure control mechanisms, which consists from enzymes to degrade proteins and to adjust blood pressure. Produced in kidney.

Note 3) Extranodal marginal zone B-cell lymphoma: A kind of lymphoma, which generally occurs in periocular tissue such as the conjunctiva and lachrymal gland. Prognosis is better than general lymphoma occurring in the eyeball, but within the adnexa oculi, it is comparatively often occurring malignant lymphoma.

Note 4) Non-Hodgkin’s B-cell lymphoma: A malignant type of lymphoma. Cells of whole body in lymph tissue become malignant.

The Matching Program for Innovations in Future Drug Discovery and Medical Care, Hokkaido University

Publicity liaison: Ms. Wada

Phone: +81-11-706-7798

E-mail: innovation@cris.hokudai.ac.jp

Involvement of the Receptor-Associated Prorenin System in the Pathogenesis of Human Conjunctival Lymphoma

(Investigative Ophthalmology & Visual Science, 2014.12.11)