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Updated: Aug 29, 2025
Organotypic Retinal Explant Cultures from Macaque Monkey
Published on: August 24, 2022
Organotypic Retinal Explant Cultures from Macaque Monkey
Wenrong Xu1, Yujie Dong1, Yan Li1
1Yunnan Eye Institute & Key Laboratory of Yunnan Province, Yunnan Eye Disease Clinical Medical Center, Affiliated Hospital of Yunnan University, Yunnan University.
Abstract:
Hereditary retinal degeneration (RD) is characterized by progressive photoreceptor cell death. Overactivation of the cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) pathway in photoreceptor cells causes photoreceptor cell death, especially in models harboring phosphodiesterase 6b (PDE6b) mutations. Previous studies on RD have used mainly murine models such as rd1 or rd10 mice. Given the genetic and physiological differences between mice and humans, it is important to understand to which extent the retinas of primates and rodents are comparable. Macaques share a high level of genetic similarity with humans. Therefore, wild-type macaques (aged 1-3 years) were selected for the in vitro culture of retinal explants that included the retina-retinal pigment epithelium (RPE)-choroid complex. These explants were treated with different concentrations of the PDE6 inhibitor zaprinast to induce the cGMP-PKG signaling pathway and simulate RD pathogenesis. cGMP accumulation and cell death in primate retinal explants were subsequently verified using immunofluorescence and the TUNEL assay. The primate retinal model established in this study may serve for relevant and effective studies into the mechanisms of cGMP-PKG-dependent RD, as well as for the development of future treatment approaches.
Insights
This study developed a primate retinal explant model to investigate hereditary retinal degeneration (RD). The model simulates RD by activating the cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) pathway, offering a more human-relevant research tool.
Area of Science:
- Ophthalmology
- Neuroscience
- Genetics
Background:
- Hereditary retinal degeneration (RD) involves progressive photoreceptor cell death.
- Overactivation of the cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) pathway contributes to photoreceptor death, particularly in models with phosphodiesterase 6b (PDE6b) mutations.
- Murine models are common for RD research, but genetic and physiological differences necessitate more comparable models.
Purpose of the Study:
- To establish an in vitro primate retinal explant model for studying hereditary retinal degeneration (RD).
- To simulate RD pathogenesis by activating the cGMP-PKG pathway in primate retinal explants.
- To provide a more human-relevant model for understanding RD mechanisms and developing treatments.
Main Methods:
- In vitro culture of retinal explants from wild-type macaques (aged 1-3 years), including the retina-retinal pigment epithelium (RPE)-choroid complex.
- Treatment of explants with zaprinast, a phosphodiesterase 6 (PDE6) inhibitor, to induce cGMP accumulation and activate the cGMP-PKG pathway.
- Verification of cGMP accumulation and cell death using immunofluorescence and the TUNEL assay.
Main Results:
- Successful establishment of an in vitro primate retinal explant model.
- Demonstrated induction of the cGMP-PKG signaling pathway and subsequent photoreceptor cell death in primate retinal explants.
- Verified cGMP accumulation and cell death using established biological assays.
Conclusions:
- A novel primate retinal explant model effectively simulates cGMP-PKG-dependent hereditary retinal degeneration (RD).
- This model offers a valuable platform for studying RD mechanisms in a context more relevant to human physiology.
- The model holds potential for evaluating future therapeutic strategies for RD.
