Organoid technology for retinal repair

Abstract

A major cause for vision impairment and blindness in industrialized countries is the loss of the light-sensing retinal tissue in the eye. Photoreceptor damage is one of the main characteristics found in retinal degeneration diseases, such as Retinitis Pigmentosa or age-related macular degeneration. The lack of effective therapies to stop photoreceptor loss together with the absence of significant intrinsic regeneration in the human retina converts such degenerative diseases into permanent conditions that are currently irreversible. Cell replacement by means of photoreceptor transplantation has been proposed as a potential approach to tackle cell loss in the retina. Since the first attempt of photoreceptor transplantation in humans, about twenty years ago, several research groups have focused in the development and improvement of technologies necessary to bring cell transplantation for retinal degeneration diseases to reality. Progress in recent years in the generation of human tissue derived from pluripotent stem cells (PSCs) has significantly improved our tools to study human development and disease in the dish. Particularly the availability of 3D culture systems for the generation of PSC-derived organoids, including the human retina, has dramatically increased access to human material for basic and medical research. In this review, we focus on important milestones towards the generation of transplantable photoreceptor precursors from PSC-derived retinal organoids and discuss recent pre-clinical transplantation studies using organoid-derived photoreceptors in context to related in vivo work using primary photoreceptors as donor material. Additionally, we summarize remaining challenges for developing photoreceptor transplantation towards clinical application.

Organ‐on‐chip models: Implications in drug discovery and clinical applications

“…Neural retinas typically last for 25 days and show limited development of inner retinal neurons and rod photoreceptors, thus limiting their use in therapeutic applications (Chen et al, ). In addition, the long culture time (up to 300 days) has impaired data collection and the ability of organoids to be used in clinical practice (Llonch et al, ). Though there is work to be done regarding the standardization of the protocol, several methods for improving organoid formation and data interpretation have recently emerged.…”

Generation of a Retina Reporter hiPSC Line to Label Progenitor, Ganglion, and Photoreceptor Cell Types

“…Current treatments for these diseases may slow the progression of retinal degeneration, but no available treatments restore lost retinal tissue. Recent advancements in 3D-culture have led to the development of retinal organoids, that consist of all major retinal cell types from human induced pluripotent stem cells (hiPSCs) 3 . This capability means that these hiPSC-derived organoids can experimentally model normal human retina development as well as onset and progression of retinal disease.…”

“…This capability means that these hiPSC-derived organoids can experimentally model normal human retina development as well as onset and progression of retinal disease. Additionally, these organoids can provide a platform to screen new drugs for the treatment or the cure of retinal disease 3,4 . Finally, hiPSCs provide the ability to make unlimited numbers of specific retinal neurons for potential transplantation therapies.…”

Special Series: Transplantation of Stem Cells into the Eye

“…Seminal work performed by the Sasai lab at the beginning of this decade has shown that retina is particularly suitable for organoids research [15]. Pluripotent stem cells (PSCs) when cultured under 3D conditions and growth factors/small molecules that promote forebrain and eye/-retina formation organize into organoids comprising all key retinal cell types, which interact with each other and form synaptic connections [16]. Notwithstanding this amazing self-organizing ability, different hiPSC lines vary in their ability to form retinal organoids in culture.…”