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Expression and Distribution of Mesencephalic Astrocyte-Derived Neurotrophic Factor in the Retina and Optic Nerve
Feng-Juan Gao1, Sheng-Hai Zhang2, Ting-Ting Li1
1Department of Ophthalmology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Abstract:
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 vitro studies 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.
Insights
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is found in the retina and optic nerve, primarily in ganglion cells. Its expression increases with hypoxia, suggesting a role in retinal ganglion cell health and disease.
Area of Science:
- Neuroscience
- Ophthalmology
- Cell Biology
Background:
- Mesencephalic astrocyte-derived neurotrophic factor (MANF), also known as ARMET, is an endoplasmic reticulum stress protein with largely unknown distribution in the retina and optic nerve.
- Understanding MANF expression is crucial for investigating its potential roles in ocular health and disease.
Purpose of the Study:
- To investigate the expression and distribution of MANF in the retina and optic nerve (ON) of rats and humans.
- To explore the cellular localization and potential regulation of MANF in retinal ganglion cells (RGCs).
Main Methods:
- Real-time PCR, immunofluorescence staining, and western blotting were employed to analyze MANF expression.
- In vitro studies were conducted to confirm MANF expression in RGCs and its subcellular localization.
- MANF expression was examined under hypoxic conditions.
Main Results:
- MANF was detected in both rat retina and ON, predominantly in the ganglion cell layer (GCL) and inner nuclear layer (INL).
- Retinal MANF levels were significantly higher than in the ON in rats.
- MANF was robustly expressed by human RGCs and partially co-localized with GFAP in the human ON.
- In vitro studies confirmed cytoplasmic localization of MANF in RGCs.
- Hypoxia induced MANF expression over time.
Conclusions:
- MANF is widely distributed in the retina and optic nerve, with significant expression in RGCs.
- MANF expression is responsive to hypoxia, indicating a potential role in RGC function and survival.
- This study enhances understanding of MANF in the context of ophthalmic diseases.
