OU Chen,SONG Houpan,XIE Wei,et al.The Effect of Ziyin Mingmu Formula (滋阴明目方) on Retinal Tissue Apoptosis and Endoplasmic Reticulum Stress in Retinitis Pigmentosa Model Mice[J].Journal of Traditional Chinese Medicine,2024,65(17):1808-1815.
OU Chen,SONG Houpan,XIE Wei,et al.The Effect of Ziyin Mingmu Formula (滋阴明目方) on Retinal Tissue Apoptosis and Endoplasmic Reticulum Stress in Retinitis Pigmentosa Model Mice[J].Journal of Traditional Chinese Medicine,2024,65(17):1808-1815.DOI: 10.13288/j.11-2166/r.2024.17.011.
The Effect of Ziyin Mingmu Formula (滋阴明目方) on Retinal Tissue Apoptosis and Endoplasmic Reticulum Stress in Retinitis Pigmentosa Model Mice
(滋阴明目方) on retinitis pigmentosa mice and its possible mechanism.
Methods
2
Sixty rd10 mice were randomly divided into model group, vitamin A group, and
Ziyin Mingmu Formula
low-, medium-, and high-dose groups, 12 mice in each group; twelve C57BL/6 mice as the blank group. The mice in
Ziyin Mingmu Formula
low-, medium-, and high-dose groups were given 13.5, 27.0 and 54.0 g/(kg·d) of
Ziyin Mingmu Formula
by gavage, respectively; mice in the Vitamin A group were given 750 IU/(kg·d) of vitamin A soft capsule by gavage; mice in the blank group and model group were given 13.5 ml/(kg·d) of physiological saline by gavage. Each group was gavaged once a day for 28 days. Fundus photography and optical coherence tomography were used to detect the morphology of the fundus and retina, TUNEL method was used to detect apoptosis, microtitre digital PCR and immunofluorescence double staining were used to detect
glucose-regulated protein 78 (GRP78), inositol-requiring enzyme 1 (IRE1), activated transcription factor 6 (ATF6), and C/EBP homologous protein (CHOP) mRNA and protein expression levels.
Results
2
In the model group, optic discs were yellowish, fundus was atrophic with large pigmentation. The retinal blood vessels were thinned, a large number of vascular white sheaths were seen, the retinal cell nuclei disorganised, and a large number of apoptotic cells were seen; the fundus conditions of the mice in all dosages of
Ziyin Mingmu Formula
and the vitamin A group were improved to varying degrees compared with those of the model group, the apoptotic cells reduced, with
Ziyin Mingmu Formula
middle- and high-dose groups showing more significant improvement. Compared with the blank group, the retinal thickness of mice in the model group reduced, and the expression of GRP78, IRE1, ATF6, CHOP mRNA and protein elevated (
P
<0.01). Compared with the model group, retinal thickness increased and GRP78, IRE1, ATF6 mRNA and protein expression decreased in the vitamin A group and
Ziyin Mingmu Formula
medium- and high-dose groups; CHOP mRNA and protein expression decreased in low-, medium-, and high-dose groups of
Ziyin Mingmu Formula
(
P
<0.05 or
P
<0.01). Compared with vitamin A group and the low-dose group of
Ziyin Mingmu Formula
, retinal thickness increased in the high-dose group of
Ziyin Mingmu Formula
(
P
<0.01). Compared with vitamin A group, GRP78, ATF6, IRE1, and CHOP mRNA expression decreased in the medium- and high-dose groups of
Ziyin Mingmu Formula
, and GRP78 and CHOP protein expression decreased (
P
<0.05 or
P
<0.01). Compared with the low-dose group of
Ziyin Mingmu Formula
, CHOP protein expression reduced in the medium- and high-dose groups of
Ziyin Mingmu Formula
(
P
<0.01).
Conclusion
2
Ziyin Mingmu Formula
can reduce apoptosis of retinal tissues by inhibiting the endoplasmic reticulum stress response, thus slowing down the progression of retinopathy and protecting visual function in a dose-dependent manner.
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SIBULESKY L , HAYES KC , PRONCZUK A , et al . Safety of <7500 RE (<25000 IU) vitamin A daily in adults with retinitis pigmentosa [J]. Am J Clin Nutr , 1999 , 69 ( 4 ): 656 - 663 .
OU C , XIE W , JIANG P , et al . Lycium barbarum L. and Salvia miltiorrhiza Bunge protect retinal pigment epithelial cells through endoplasmic reticulum stress [J]. J Ethnopharmacol , 2022 , 296 : 115519 . doi: 10.1016/j.jep.2022.115519 http://dx.doi.org/10.1016/j.jep.2022.115519 .
KANG K , YU M . Protective effect of sulforaphane against retinal degeneration in the Pde6(rd10) mouse model of retinitis pigmentosa [J]. Curr Eye Res , 2017 , 42 ( 12 ): 1684 - 1688 .
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