Expression and Distribution of Mesencephalic Astrocyte-Derived Neurotrophic Factor in the Retina and Optic Nerve.
Mesencephalic astrocyte-derived neurotrophic factor (MANF), otherwise named Arginine-Rich, Mutated in Early-stage Tumors (ARMET), is a secretory endoplasmic reticulum stress (ERS) protein that is widely expressed in mammalian tissues. To date, little is known about the distribution and expression of MANF in the retina and optic nerve (ON). Therefore, we studied the expression and distribution of MANF in the ON and retina by real-time PCR, immunofluorescence staining and western blotting. Results from rat and mouse were highly consistent in the retina. MANF was detected in both tissues in rat, wherein it was principally localized to the ganglion cell layer (GCL), followed by the inner nuclear layer (INL). The MANF protein levels in the rat retina were 3.33-fold higher than in the rat ON. Additionally, MANF was robustly expressed by retinal ganglion cells (RGCs) in the human retina. In human ON, MANF was partially co-localized with glial fibrillary acidic protein (GFAP), suggesting that it was not restricted to astrocytes.In vitrostudies confirmed that MANF could be robustly expressed in RGCs and was found principally within the cytoplasm. Hypoxia can stimulate up-regulation by of MANF expression over time, suggesting that MANF may play a vital role in the functional regulation of RGCs both in health and disease. We believe that the present study improves our understanding of the distribution and expression of MANF in the retina and ON and could help in further analysis of its interact and correlate with the relevant ophthalmic diseases.
Department of Ophthalmology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Feng-Juan
FJ
Gao
Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan UniversityShanghai, China; Shanghai Key Laboratory of Visual Impairment and RestorationShanghai, China; Key Laboratory of Myopia, Ministry of Health, Fudan UniversityShanghai, China.
Sheng-Hai
SH
Zhang
Department of Ophthalmology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Ting-Ting
TT
Li
Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan UniversityShanghai, China; Shanghai Key Laboratory of Visual Impairment and RestorationShanghai, China; Key Laboratory of Myopia, Ministry of Health, Fudan UniversityShanghai, China.
Ji-Hong
JH
Wu
Department of Ophthalmology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Qiang
Q
Wu
distribution; mesencephalic astrocyte-derived neurotrophic factor; optic nerve; retina; retinal ganglion cells