Amelioration of Functional, Metabolic, and Morphological Deterioration in the Retina following Retinal Detachment by Green Tea Extract

Antioxidants · 6 authors, 2 centres

AI SUMMARY

FIDELITY 100%

POPULATIONFemale Sprague Dawley rats (6–8 weeks old, ~250 g) with induced retinal detachment

INTERVENTIONOral green tea extract (GTE) at doses of 142.9 mg/kg, 275 mg/kg, or 550 mg/kg (containing 96.3, 185.3, or 370.6 mg/kg EGCG, respectively) administered twice daily for three days starting four hours after RD induction

COMPARISONRetinal detachment (RD) group receiving water only; non-RD group (sham injection)

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TL;DR

In a rat model of retinal detachment, oral administration of a low dose (142.9 mg/kg) of green tea extract (GTE) for three days significantly preserved retinal function, reduced edema, and decreased apoptosis compared to untreated detachment. GTE exerted anti-oxidative, anti-inflammatory, and metabolic effects, including suppression of HIF-1α, reduction of pro-inflammatory cytokines like CCL2, and modulation of lipid metabolism. These findings suggest GTE could be a potential pharmacological intervention to minimize retinal damage during the critical waiting period before surgical reattachment.

Full summary

3,655 CHARS

**Background:** Retinal detachment (RD) deprives the neurosensory retina of oxygen and nutrients, leading to hypoxia, oxidative stress, inflammation, and apoptosis. Surgical reattachment is the only treatment, but delays of up to several weeks are common, and no pharmacological intervention exists to protect the retina during this waiting period. Green tea extract (GTE) has known anti-oxidative, anti-inflammatory, and anti-apoptotic properties. This study investigated whether oral GTE could mitigate retinal damage in a rat RD model.

**Methods:** Retinal detachment was induced in female Sprague Dawley rats by subretinal injection of 2 µL of 1% sodium hyaluronate. Four hours later, rats received oral GTE (Theaphenon E®, containing 70% EGCG) at various doses twice daily for three days. Two batches were tested: Batch 1 compared non-RD, RD, GTE 142.9 mg/kg (96.3 mg/kg EGCG), EGCG 96.3 mg/kg, and EGCG 352.2 mg/kg; Batch 2 compared non-RD, RD, GTE 275 mg/kg (185.3 mg/kg EGCG), and GTE 550 mg/kg (370.6 mg/kg EGCG). Outcomes included electroretinography (ERG) scotopic and photopic a- and b-wave amplitudes, normalized outer nuclear layer (ONL) thickness (using INL as control), TUNEL staining for apoptosis, ELISA for caspase-3, sphingomyelin, protein carbonyl, and HIF-1α, cytokine array of vitreous humor, and GC/MS for retinal fatty acid and cholesterol levels.

**Key Results:** The low dose of GTE (142.9 mg/kg) showed significant protective effects. Normalized ONL thickness was significantly reduced compared to RD (82.4 ± 8.2% of RD in Batch 1, p < 0.05; 66.0 ± 8.2% in Batch 2, p < 0.05), approaching non-RD levels (83.5 ± 4.7%). ERG scotopic a- and b-wave amplitudes and photopic b-wave amplitude were significantly higher in the low-dose GTE group than in RD (p < 0.05), with scotopic a-wave and photopic b-wave amplitudes similar to non-RD. Higher GTE doses (275 and 550 mg/kg) and EGCG alone (96.3 and 352.2 mg/kg) did not improve ERG amplitudes and sometimes worsened them. TUNEL-positive cells were significantly reduced in the low-dose GTE group compared to RD (p < 0.0001). Caspase-3 levels remained elevated in the GTE group, but sphingomyelin levels were significantly decreased (p < 0.05). Protein carbonyl content (oxidative stress marker) and HIF-1α levels were significantly lower in the GTE group than in RD (p < 0.05). Cytokine array revealed that RD increased pro-inflammatory cytokines (CCL2, CCL20), GDF-15, OPN, MMP3, serpin E1, and metabolic regulators (adiponectin, DPPIV, IGF-1, IGFBP-3) by >2.5-fold. GTE treatment significantly reduced CCL2, serpin E1, adiponectin, DPPIV, IGF-1, and IGFBP-3, while increasing IL-13 and IL-1α. Free fatty acids increased >30-fold after RD, but GTE did not significantly alter this. Cholesterol levels did not differ among groups.

**Clinical Implications:** This study provides the first evidence that oral GTE can protect the retina during the critical three-day window after RD, preserving function and structure. The effective dose (142.9 mg/kg in rats) corresponds to approximately 0.984 g EGCG equivalent twice daily in humans, which is below the well-tolerated dose in phase II clinical trials. GTE's mechanisms include anti-oxidation (reducing protein carbonyl and HIF-1α), anti-inflammation (suppressing CCL2, increasing IL-13), anti-apoptosis (reducing sphingomyelin and TUNEL-positive cells), and metabolic modulation (lowering adiponectin, DPPIV, IGF-1). These findings suggest GTE could be a safe, readily available oral supplement to minimize retinal damage while patients await surgery, potentially improving visual outcomes. Further clinical studies are warranted.

PICO

PPOPULATION

Female Sprague Dawley rats (6–8 weeks old, ~250 g) with induced retinal detachment

IINTERVENTION

Oral green tea extract (GTE) at doses of 142.9 mg/kg, 275 mg/kg, or 550 mg/kg (containing 96.3, 185.3, or 370.6 mg/kg EGCG, respectively) administered twice daily for three days starting four hours after RD induction

OOUTCOME

Retinal function (ERG a- and b-wave amplitudes), retinal morphology (normalized ONL thickness), apoptosis (TUNEL-positive cells, caspase-3), oxidative stress (protein carbonyl, HIF-1α), inflammation (cytokine array), and metabolism (sphingomyelin, fatty acids, cholesterol)

STUDY TYPE

other

SPECIALTY

ophthalmology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10886023

Amelioration of Functional, Metabolic, and Morphological Deterioration in the Retina following Retinal Detachment by Green Tea Extract

Antioxidants

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ABSTRACT

Abstract Retinal detachment (RD) can result in the loss of photoreceptors that cause vision impairment and potential blindness. This study explores the protective effects of the oral administration of green tea extract (GTE) in a rat model of RD. Various doses of GTE or epigallocatechin gallate (EGCG), the most active ingredient in green tea catechins, were administered to Sprague Dawley (SD) rats with experimentally induced retinal detachment. The rats received sub-retinal injections of hyaluronic acid (0.1%) to induce RD and were given different doses of GTE and EGCG twice daily for three days. Notably, a low dose of GTE (142.9 mg/kg) caused significantly higher signal amplitudes in electroretinograms (ERGs) compared to higher GTE doses and any doses of EGCG. After administration of a low dose of GTE, the outer nuclear layer thickness, following normalization, of the detached retina reduced to 82.4 ± 8.2% (Mean ± SEM, p < 0.05) of the thickness by RD treatment. This thickness was similar to non-RD conditions, at 83.5 ± 4.7% (Mean ± SEM) of the thickness following RD treatment. In addition, the number of TUNEL-positive cells decreased from 76.7 ± 7.4 to 4.7 ± 1.02 (Mean ± SEM, p < 0.0001). This reduction was associated with the inhibition of apoptosis through decreased sphingomyelin levels and mitigation of oxidative stress shown by a lowered protein carbonyl level, which may involve suppression of HIF-1α pathways. Furthermore, GTE showed anti-inflammatory effects by reducing inflammatory cytokines and increasing resolving cytokines. In conclusion, low-dose GTE, but not EGCG, significantly alleviated RD-induced apoptosis, oxidative stress, inflammation, and energy insufficiency within a short period and without affecting energy metabolism. These findings suggest the potential of low-dose GTE as a protective agent for the retina in RD. Keywords: retinal detachment, green tea extract, apoptosis, oxidative stress, inflammation, metabolism, antioxidant, epigallocatechin gallate

CITATION EXPORT

Kai On Chu, Yolanda Wong Ying Yip, Kwok Ping Chan et al.. Amelioration of Functional, Metabolic, and Morphological Deterioration in the Retina following Retinal Detachment by Green Tea Extract. Antioxidants. (2024). https://doi.org/10.3390/antiox13020235

AUTHORS

6 · 2 CENTRES

Kai On Chu, Yolanda Wong Ying Yip, Kwok Ping Chan, Chi Chiu Wang, Danny Siu Chun Ng, Chi Pui Pang

1Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China; [email protected] (K.O.C.); [email protected] (Y.W.Y.Y.); [email protected] (K.P.C.)
2Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, China; [email protected]