SEARCHOTHERophthalmology, retina

other·ophthalmology, retina, preclinical research, biomedical research·PMC10805728

The temporal progression of retinal degeneration and early-stage idebenone treatment in the Pde6b rd1/rd1 mouse model of retinal dystrophy

Scientific Reports · 7 authors, 4 centres

AI SUMMARY

FIDELITY 100%

POPULATIONPde6b rd1/rd1 mice and wild-type mice at early postnatal developmental stages

INTERVENTIONEarly-stage oral idebenone administration (dose adjusted from 900 mg/day clinical LHON dose for body surface area)

COMPARISONWild-type mice and untreated rd1/rd1 mice

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

“

TL;DR

This preclinical study characterized the temporal progression of retinal degeneration in Pde6b rd1/rd1 mice from birth through P14 and found that early oral idebenone treatment at P14 extended photoreceptor survival and enhanced retinal synaptogenesis, while late treatment at P21 showed no benefit.

Full summary

987 CHARS

This preclinical study examined the temporal progression of retinal degeneration in Pde6b rd1/rd1 mice from birth through P14, focusing on early predegenerative changes. Ultrastructural analysis identified mitochondrial damage in developing rd1 rod photoreceptors as early as P3, preceding substantial photoreceptor loss. A significant difference in pde6b mRNA expression between rd1 and wild-type mice was observed from P3 onwards. Despite normal morphological appearance, second-order neurons in rd1 retinas never established normal synaptic contacts. Oral administration of idebenone at P14 extended photoreceptor cell survival and enhanced retinal second-order synaptogenesis, while treatment at P21 yielded no substantial improvement. The authors propose that mitochondrial damage serves as an early driver of photoreceptor cell death, and that organelles including mitochondria, Golgi apparatus, and endoplasmic reticulum may have reciprocal influences during retinal degeneration.

PICO

PPOPULATION

Pde6b rd1/rd1 mice and wild-type mice at early postnatal developmental stages

IINTERVENTION

Early-stage oral idebenone administration (dose adjusted from 900 mg/day clinical LHON dose for body surface area)

OOUTCOME

Photoreceptor cell survival, retinal synaptogenesis, mitochondrial morphology, pde6b mRNA expression, and visual acuity

STUDY TYPE

other

SPECIALTY

ophthalmology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10805728

The temporal progression of retinal degeneration and early-stage idebenone treatment in the Pde6b rd1/rd1 mouse model of retinal dystrophy

Scientific Reports

READ THE FULL PAPER

ABSTRACT

Abstract Photoreceptor cell death, primarily through apoptosis, related to retinal disorders like retinitis pigmentosa (RP), would result in vision loss. The pathological processes and crucial mutant conditions preceding photoreceptor cell demise are not well understood. This study aims to conduct an in-depth examination of early-stage changes in the widely utilized Pde6b rd1/rd1 (rd1) mouse model, which has Pde6b gene mutations representing autosomal recessive RP disorder. We investigated the morphology and ultrastructure of retinal cells, including second-order neurons, during the initial phase of disease progression. Our findings revealed that mitochondrial alterations in rod photoreceptors were present as a predeath mutant state as early as postnatal day 3 (P3). The bipolar and horizontal cells from the rd1 mouse retina exhibited significant morphological changes in response to loss of photoreceptor cells, indicating that second-order neurons rely on these cells for their structures. Subsequent oral administration of idebenone, a mitochondria-protective agent, enhanced retinal function and promoted both photoreceptor cell survival and inner retinal second-order synaptogenesis in rd1 mice at P14. Our findings offer a mechanistic framework, suggesting that mitochondrial damage acts as an early driver for photoreceptor cell death in retinal degeneration. Subject terms: Experimental models of disease, Disease model, Hereditary eye disease, Retinal diseases

CITATION EXPORT

Lei Zhang, Wei Liu, Hai-Yan Wang et al.. The temporal progression of retinal degeneration and early-stage idebenone treatment in the Pde6brd1/rd1 mouse model of retinal dystrophy. Scientific Reports. (2024). https://doi.org/10.1038/s41598-024-52391-y

AUTHORS

7 · 4 CENTRES

Lei Zhang, Wei Liu, Hai-Yan Wang, Wei Qiang, Ru Wang, Zhi-Li Cui, Zuo-Ming Zhang

1Shaanxi Eye Hospital, Xi’an People’s Hospital (Xi’an Fourth Hospital), Xi’an, 710004 China
2Xi’an Key Laboratory of Digital Medical Technology of Ophthalmologic Imaging, Xi’an People’s Hospital (Xi’an Fourth Hospital), Xi’an, 710004 China
3Medical Experiment Center, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province China
4Department of Clinical Medicine, Faculty of Aerospace Medicine, Air Force Medical University, Xi’an, 710032 Shaanxi Province China