Recently, a study published in Scientific Reports (Sci Rep) revealed the significant efficacy and multitarget mechanisms of Ganoderma lucidum polysaccharides (GLPs), the core bioactive components of the traditional Chinese medicinal mushroom Ganoderma lucidum, in the prevention and treatment of retinal ischemia–reperfusion injury (RIRI). Using a rat model of RIRI, the study demonstrated that GLPs (35, 70, and 140 mg/kg/day) dose-dependently alleviated retinal histopathological damage and cellular apoptosis, while effectively restoring retinal electroretinogram function.
The protective mechanisms of GLPs involved activation of the Nrf2/HO-1 antioxidant signaling pathway to counteract oxidative stress; suppression of excessive activation of astrocytes and microglia to mitigate neuroinflammation; regulation of connexin 43 (Cx43) and aquaporin 4 (AQP4) expression to maintain neurovascular unit homeostasis; and modulation of the HIF-1α/VEGF and Notch signaling pathways to improve retinal blood flow density and preserve the integrity of the blood–retinal barrier.
These findings indicate that GLPs provide comprehensive protection of the retinal neurovascular unit through synergistic multi-pathway actions, offering a highly promising natural candidate strategy for the prevention and treatment of ischemic retinal diseases such as glaucoma and diabetic retinopathy.
Retinal ischemia–reperfusion injury can be likened to the retina experiencing hypoxic “suffocation” followed by a secondary insult upon restoration of blood flow. This process triggers a cascade of pathological events, including oxidative stress and inflammatory responses, ultimately disrupting retinal structure and leading to irreversible visual impairment. As the retinal neurovascular unit represents the core structural foundation for visual function, disruption of its homeostasis is a key driving factor in such injuries.
Recently, a study published in Scientific Reports brought a breakthrough in this field. The core bioactive component of the traditional Chinese medicinal herb Ganoderma lucidum, Ganoderma lucidum polysaccharides, was confirmed to protect the retina through multiple mechanisms and to reverse ischemia–reperfusion injury, illuminating new hope for restoring visual clarity in patients with ocular diseases.
Experimental Design and Protective Effects of Ganoderma lucidum Polysaccharides
The research team used postnatal day 6 Sprague–Dawley rats as experimental subjects and established a retinal ischemia–reperfusion injury model via anterior chamber perfusion. Subsequently, rats received oral administration of Ganoderma lucidum polysaccharides for seven consecutive days at doses of 35, 70, and 140 mg/kg/day. A comprehensive evaluation of the protective effects of GLPs was conducted using histological, electrophysiological, and molecular biological techniques.
The results demonstrated that Ganoderma lucidum polysaccharides exerted significant protective effects against ischemia–reperfusion-induced retinal damage. At a dose of 70 mg/kg, GLPs effectively alleviated retinal thinning and laminar structural disorganization, reduced the number of TUNEL-positive apoptotic cells, and markedly reversed the thickness reduction of the inner plexiform layer and inner nuclear layer.
At a dose of 140 mg/kg, GLPs significantly upregulated Nrf2 and HO-1 protein expression in retinal tissues, increased superoxide dismutase activity, and reduced malondialdehyde levels. Through activation of the Nrf2/HO-1 antioxidant pathway, GLPs efficiently counteracted oxidative stress–induced damage.
Ganoderma lucidum polysaccharides alleviate retinal pathological damage induced by retinal ischemia–reperfusion injury
In retinal functional assessments, GLP intervention led to pronounced recovery of retinal function. Visual electrophysiological testing showed that, under different stimulus intensities, the amplitudes of both a-waves and b-waves in the electroretinograms of GLP-treated rats were significantly enhanced and increased with rising stimulus intensity. The a-wave reflects photoreceptor function, while the b-wave reflects secondary neuronal function, indicating that GLPs comprehensively restored signal transmission across multiple retinal neuronal layers. In addition, the amplitude of the photopic negative response, which is directly associated with retinal ganglion cell function, was significantly increased, confirming that GLPs provide substantial protection to retinal ganglion cells affected by ischemia–reperfusion injury.
Ganoderma lucidum polysaccharides attenuate oxidative stress induced by retinal ischemia–reperfusion injury and restore retinal function
Immunofluorescence staining revealed that ischemia–reperfusion injury markedly increased immunopositivity of the astrocyte marker GFAP and the microglial marker IBA-1, accompanied by enlargement of glial cell bodies and induction of reactive gliosis. Treatment with 70 mg/kg and 140 mg/kg Ganoderma lucidum polysaccharides significantly downregulated the expression of both markers, inhibiting excessive proliferation and activation of glial cells and preventing further damage to the retinal neurovascular unit.
In addition, retinal ischemia–reperfusion injury led to downregulation of connexin 43 (Cx43) expression and upregulation of aquaporin 4 (AQP4) expression. Ganoderma lucidum polysaccharides dose-dependently modulated the protein and mRNA levels of both molecules, restoring internal material and information exchange pathways within the neurovascular unit and maintaining retinal microenvironmental homeostasis.
Ganoderma lucidum polysaccharides inhibit glial cell proliferation in the retinas of rats with retinal ischemia–reperfusion injury
Optical coherence tomography angiography revealed that rats in the ischemia–reperfusion injury group exhibited retinal vascular dilation and tortuosity, significantly reduced capillary perfusion density, and markedly decreased mean retinal blood flow density. Following Ganoderma lucidum polysaccharide treatment, vascular tortuosity was noticeably reduced, and mean retinal blood flow density was significantly increased in the 70 mg/kg and 140 mg/kg groups, indicating effective restoration of capillary perfusion.
Molecular mechanism analyses showed that GLPs downregulated ischemia–reperfusion-induced expression of VEGF, HIF-1α, and Notch proteins, while upregulating the mRNA levels of VE-cadherin and endothelial nitric oxide synthase. By inhibiting the HIF-1α–VEGF and Notch signaling pathways, GLPs stabilized endothelial cell junctions, reduced vascular dilation and neovascularization, and thereby preserved the integrity of the blood–retinal barrier.
Effects of Ganoderma lucidum polysaccharides on retinal vascular morphology and function in rats with retinal ischemia–reperfusion injury
This study revitalizes the role of the traditional Chinese medicinal herb Ganoderma lucidum in modern medical research. As a medicinal and edible material used for thousands of years, Ganoderma lucidum contains polysaccharides that exhibit strong potential for ocular protection. Through multiple synergistic mechanisms, these polysaccharides activate antioxidant pathways to resist oxidative damage, suppress glial proliferation, stabilize vascular endothelial function, and regulate intercellular communication channels, thereby comprehensively preserving the structural and functional integrity of the retinal neurovascular unit.
For ocular diseases such as glaucoma and diabetic retinopathy, in which retinal ischemia–reperfusion injury represents a core pathological basis, the properties of Ganoderma lucidum polysaccharides position them as promising therapeutic candidates. With further research, this natural bioactive compound derived from traditional Chinese medicine may open new avenues in visual health protection, offering renewed therapeutic hope to patients with ocular diseases and helping more individuals avoid vision loss.