Page 94 - Read Online

Page 192 Ma et al. J Transl Genet Genom 2022;6:179-203 https://dx.doi.org/10.20517/jtgg.2021.48

myopia. In patients with high myopic macular hole, the anatomical closure of the macular hole and visual
improvements have been the main criteria for a successful surgery. There are reports that failed to improve
[181]
visual acuity after the closure of macular hole . Ophthalmologists are inclined to attribute the failure to
the severity of pathologic myopia or disrupted photoreceptors [182,183] . However, the status of RPE was ignored
in the past.

[184]
More attention needs to be paid to RPE. Fang et al. studied 14 eyes with fovea-centered macular atrophy
that developed after successful pars plana vitrectomy (PPV) for myopic traction maculopathy and macular
hole retinal detachment. The postoperative visual acuity was even worse than the baseline. These eyes had
diffused atrophy or extrafoveal patchy atrophy preoperatively and developed macular atrophy at a median
time of 3.5 months after surgery. PPV-related macular atrophy is different from CNV- or patchy atrophy-
related macular atrophy as it starts from the fovea. Eyes with macular hole retinal detachment are prone to
develop PPV-related macular atrophy. This study emphasized the importance of RPE on the recovery of
vision. When reviewing the postoperative outcomes of high myopic macular hole, AL > 30 mm and
presence of posterior staphyloma are risk factors for unfavorable visual outcomes . It is rational that a
[185]
longer AL indicates severe chorioretinal atrophy and loss of RPE.

Therefore, transplantation of RPE cells seems a preferable way to improve the visual outcomes of high
myopic patients by replacing atrophic RPE cells with healthy ones. The efficiency and safety of GMP-grade
human iPSC-RPE were proved in a pre-clinical study conducted by Zhang et al. . Here, the transplanted
[172]
cells were injected into the subretinal space. However, a cell suspension is not practical to apply in myopic
macular hole surgery. Scaffolds for RPE transplantation with excellent cytocompatibility and
biocompatibility are required . A cell patch is feasible to place under the macular hole during PPV
[174]
surgery. The scaffolds act as the Bruch’s membrane for functional RPE reconstruction [Figure 3]. Compared
with traditional surgery, combination with iPSC-RPE transplantation would reap greater benefits. One
concern of RPE cell patch transplantation is the viability of the cell patch when there is a lack of choroidal
perfusion from the severely atrophic choroid. Pang et al. , in 2015, identified that myopic eyes with an
[186]
extremely thin choroid (≤ 20 μm) could still have BCVA ≥ 20/40. They proposed two explanations: (1) a
fovea with extremely thin choroid would receive blood supply from larger patent choroidal vessels located
eccentric to the subfoveal area; and (2) an atrophic retina with a thinner layer allows more oxygen to
permeate from deep capillary plexus to outer retina. Therefore, we have reasons to believe that
transplantation of RPE cell patches to eyes with myopic macular holes is feasible.

Fibroblasts/Myofibroblasts
The sclera, as the wall of eye globe, must have the strength to protect the delicate intraocular structures and
some degree of elasticity to buffer fluctuations of intraocular pressure. The sclera is composed of collagens,
proteoglycans, non-collagenous glycoproteins, and elastic fibers. In the human sclera, 90% of the
components are collagen type I . The collagens form the scaffolds, while proteoglycans and glycoproteins
[187]
fill the interfibrillar space . Collagen fibrils irregularly arrange and form layers. Fibroblasts intersperse
[188]
between scleral collagen layers and synthesize sclera extracellular matrix components .
[189]
The thinning of sclera is a pivotal factor in the progression of myopia. In the histological study of enucleated
human eye globes, the scleral volume increases with longer AL in the first two years of life and stays stable
in the following years . This finding indicates that scleral thinning due to axial elongation is contributed
[190]
to the rearrangement of existing sclera tissue rather than synthesizing new sclera. In the posterior sclera of
[191]
myopic eye, reductions in the number of fibroblasts and the collagen fibril diameter can be found . In
addition, unusual fibrils with a star shape on cross section increase in myopic sclera . It is known that an
[191]