| Project/Area Number |
25670230
|
|---|
| Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
KANEKO Hiroki 名古屋大学, 医学(系)研究科(研究院), 助教 (20647458)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KACHI Shu 名古屋大学, 医学部附属病院, 講師 (30345904)
|
|---|
| Project Period (FY) |
2013-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
|
|---|
| Keywords | 加齢黄斑変性 / ヒスタミン受容体 / 脈絡膜新生血管 / 抗血管新生 / マクロファージ / 血管内皮増殖因子 / ヒスタミンh4受容体 |
|---|
| Outline of Final Research Achievements |
We examined the therapeutic efficacy of reducing histamine receptor h4 (HRH4) expression in choroidal neovascularizations (CNVs) for the treatment of age-related macular degeneration (AMD).
Human HRH4 was confirmed only in CNV samples from AMD patients and not in the other subretinal tissues. Mouse HRH4 was expressed in the retinal pigment epithelium (RPE) only after inducing laser-CNV in wild-type mice, and it was co-localized with the macrophage marker F4/80. Laser-CNV volume was reduced in Hrh4-/- mice compared with that in wild-type mice, and JNJ7777120 successfully suppressed laser-induced CNV volume and pathological CNV leakage in wild-type mice. The eyes injected with JNJ7777120 did not show retinal degeneration. HRH4 was expressed in macrophages that accumulated around CNVs. Suppressing HRH4 expression led to the prevention of pathological vessel leakage without showing retinal toxicity, indicating that HRH4 has potential as a novel therapeutic target in AMD.
|
