title: Iris Pigmented Epithelial Stem Cells as a Strategy to Treat Age-related Macular Degeneration
Creators: name: Pied, Valentin
Publisher: name: University of Liverpool Repository
Year: 2024

description: The existence of iris pigmented epithelial stem cells has been hypothesised in the end of 
the 90s when ophthalmologists and scientists started to compare the iris pigmented 
epithelium (IPE) and the retinal pigmented epithelium (RPE). Early investigations 
demonstrated functional similarities between both tissues in various models, in which IPE 
cells were able to integrate the RPE without subsequent issues and proved RPE rescue 
effect. Over investigations, IPE cells demonstrated a certain phenotypic plasticity as 
neurons and photoreceptors were also generated in vitro. These early works brought the 
possibility that IPE cells could replace RPE cells in non-exudative age-related macular 
degeneration (AMD), a progressive and permanent loss of vision without therapeutic 
options until our days. However, no IPE stem cells were identified so far and their 
existence remain hypothetic until today. 
Stem cells therapies aim to replace degraded tissues with cell grafts developed in vitro. 
Intense research is dedicated to develop RPE grafts with some clinical trials already 
completed, which demonstrated abilities to stabilise the vision. Therefore, the 
identification of IPE stem cells is of interest in a clinical perspective as it is biologically 
close to the RPE, so potential development would not have prohibitive cost while a 
therapy could be developed in a personalised manner, so the patient would provides its 
own stem cells to treat its affection. 
Histological investigations defined some native features of the porcine IPE. Smooth 
muscle proteins composed the anterior layer, conjugated with a global flexible 
cytoskeleton. The basal lamina surrounds the porcine IPE, its composition varying 
according to the cell functions. Finally, cell proliferation occurs mainly in and near the 
ciliary body-IPE junction, where proteins associated with multipotency were observed. 
IPE cells were then processed in vitro as neurospheres. Spheres obtained were resulting 
from cell aggregation and not clonal proliferation. Specific neuronal proteins were 
observed in some aggregates. Follow-up investigations revealed the upregulation of cell 
transformation-associated pathways and the downregulation of RPE development associated ones after the switch from generic FBS &amp; adherent-based conditions to a 
specific neurosphere culture environment. Neuronal cell culture using B27 supplement 
was then used. Four subsequent cell types were commonly observed: epithelial-like 
cells/fibroblasts-like, neurons-like and a third undefined group. Small epithelial-like cells 
morphologically close to induced-pluripotent stem cells (iPSC) were observed in medium 
supplemented with 2X B27. However, lab constraints did not allow to characterise them 
more.
Collectively, these data confirmed that the porcine IPE tissue conducts smooth muscular 
functions in vivo. The tissue seems to preserve its homeostasis by maintaining 
proliferation in its periphery, where cells express neuronal multipotent-associated 
proteins. The ability to transform into other cells was then observed in vitro. No stem cells 
were identified but further investigations shall follow this work as the small epithelial-like 
may be IPE stem cells.