Stem Cell-Based Therapy for Diseases of the Retinal Pigment Epithelium: From Bench to Bedside

Sachdeva, Mira M.; Eliott, Dean

doi:10.3109/08820538.2015.1115253

Cited by 26 publications

(18 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Injection of healthy retinal pigment epithelium (RPE) cells into the subretinal space of eyes with age-related macular degeneration (AMD) and Stargardt's macular dystrophy is being studied as a therapy to prevent or reverse photoreceptor injury, as evidence suggests that dysfunction and loss of the RPE leads to photoreceptor damage and vision loss in these diseases. 1 – 4 More recently, clinical trials involving subretinal injections of viral vectors as gene therapy for retinitis pigmentosa, 5 Leber's congenital amaurosis. 6 , 7 and Leber's hereditary optic neuropathy 8 have been conducted.…”

Section: Introductionmentioning

confidence: 99%

Volumetric Measurement of Subretinal Blebs Using Microscope-Integrated Optical Coherence Tomography

Hsu

Gabr

Viehland

et al. 2018

Trans. Vis. Sci. Tech.

View full text Add to dashboard Cite

PurposeWe advance studies of subretinal treatments by developing a microscope-integrated optical coherence tomography (MIOCT) image-based method for measuring the volume of therapeutics delivered into the subretinal space.MethodsA MIOCT image-based volume measurement method was developed and assessed for accuracy and reproducibility by imaging an object of known size in model eyes. This method then was applied to subretinal blebs created by injection of diluted triamcinolone. Bleb volumes obtained from MIOCT were compared to the intended injection volume and the surgeon's estimation of leakage.ResultsValidation of the image-based volume measurement method showed accuracy to ±1.0 μL (6.0% of measured volume) with no statistically significant variation under different imaging settings. When this method was applied to subretinal blebs, four of 11 blebs without surgeon-observed leakage yielded a mean volume of 32 ± 12.5 μL, in contrast to the intended 50 μL volume injected from the delivery device. This constituted a mean difference of −18 μL (mean percent error, 36 ± 25%). For all 11 blebs, the surgeon's estimations of leakage were significantly different from and showed no correlation with the volume loss based on image-based volume measurements (P < 0.001, paired t-test; intraclass correlation = 0).ConclusionsWe validated an accurate and reproducible method for measuring subretinal volumes using MIOCT. Use of this method revealed that the intended volume might not be delivered into the subretinal space. MIOCT can allow for accurate assessment of subretinal dose delivered, which may have therapeutic implications in evaluating the efficacy and toxicity of subretinal therapies.Translational RelevanceUse of MIOCT can provide feedback on the accuracy of subretinal injection volumes delivered.

show abstract

Section: Introductionmentioning

confidence: 99%

Volumetric Measurement of Subretinal Blebs Using Microscope-Integrated Optical Coherence Tomography

Hsu

Gabr

Viehland

et al. 2018

Trans. Vis. Sci. Tech.

View full text Add to dashboard Cite

show abstract

“…In many ocular tissues, stem/progenitor cell-based therapies have become a highly promising approach to treating diseases previously considered incurable. 1 – 5 Similar to other exocrine glands, including the pancreas, salivary, and mammary glands, the “healthy” adult LG has a high regenerative capacity and is able to repair itself even after substantial damage. 6 – 9 Recently, replacement of an adult mouse LG with an embryonic LG-derived epithelio-mesenchymal reaggregate or epithelial cell progenitors has been demonstrated.…”

mentioning

confidence: 99%

Manipulation of Panx1 Activity Increases the Engraftment of Transplanted Lacrimal Gland Epithelial Progenitor Cells

Basova

Tang

Umasume

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PurposeSjögren's syndrome is a systemic chronic autoimmune inflammatory disease that primarily targets the salivary and lacrimal glands (LGs). Currently there is no cure; therefore, cell-based regenerative therapy may be a viable option. LG inflammation is facilitated by extracellular ATP and mediated by the Pannexin-1 (Panx1) membrane channel glycoprotein. We propose that suppression of inflammation through manipulation of Panx1 activity can stimulate epithelial cell progenitor (EPCP) engraftment.MethodsThe expression of pannexins in the mouse and human LG was assayed by qRT-PCR and immunostaining. Acute LG inflammation was induced by interleukin-1α (IL1α) injection. Prior to EPCP transplantation, IL1α-injured or chronically inflamed LGs of thrombospondin-1–null mice (TSP-1−/−) were treated with the Panx1-specific blocking peptide (10panx) or the self-deliverable RNAi (sdRNAi). The efficacy of cell engraftment and the area of inflammation were analyzed by microscopy.ResultsPanx1 and Panx2 were detected in the mouse and human LGs. Panx1 and proinflammatory factors were upregulated during acute inflammation at days 1 to 3 after the IL1α injection. The analysis of EPCP engraftment demonstrated a significant and reproducible positive correlation between the 10panx peptide or Panx1 sdRNAi treatment and the number of engrafted cells. Similarly, treatment of the LG of the TSP-1−/− mouse (mouse model of chronic LG inflammation) by either Panx1 or Caspase-4 (also known as Casp11) sdRNAi showed a significant decrease in expression of proinflammatory markers and the lymphocyte infiltration.ConclusionsOur results suggest that blocking Panx1 and/or Casp4 activities is a beneficial strategy to enhance donor cell engraftment and LG regeneration through the reduction of inflammation.

show abstract

“…An emerging approach to address AMD is RPE cell replacement therapy. RPE cells derived from human embryonic stem cells or human‐induced pluripotent stem cells are being evaluated in preclinical studies and clinical trials for their potential to rescue the damaged retina (Carr et al, ; Kamao et al, ; Mandai et al, ; M'Barek et al, ; Schwartz et al, ; Sachdeva & Eliott, ; Schwartz et al, ; Schwartz, Tan, Hosseini, & Nagiel, ; Song et al, ; Sowden, ; Wang, Stern, & Temple, ). Although pluripotent stem cells are a promising source of RPE cells due to their unlimited self‐renewal and differentiation potential (Assawachananont et al, ; Idelson et al, ; Krohne et al, ), they may not function on Bruch's membrane identically to native RPE cells (Sugino et al, ).…”

Section: Discussionmentioning

confidence: 99%

Screening and optimization of potential injection vehicles for storage of retinal pigment epithelial stem cell before transplantation

Tian

Davis

Zonca

et al. 2018

J Tissue Eng Regen Med

View full text Add to dashboard Cite

Retinal pigment epithelial (RPE) cells are highly specialized neural cells that have several functions essential for vision. Progressive deterioration of RPE cells in elderly individuals can result in visual impairment and ultimately the blinding disease agerelated macular degeneration. Subretinal transplantation of stem cell-derived RPE cell suspensions is being explored as a strategy to recover the damaged retina and improve vision. This approach may be improved by developing a vehicle that increases postinjection cell viability and distribution and integration of RPE cells. In this study, Food and Drug Administration-approved natural polymers, including alginate, methylcellulose, and hyaluronic acid (HA), were examined for performance as cell vehicles for adult human RPE stem cells (RPESCs). We compared the effect of RPESC storage as a cell suspension in these delivery vehicles for 1-96 hr at different temperatures on subsequent cell performance in a cell culture model. RPESC survival, attachment, distribution, proliferation, and differentiation into RPE cells were monitored by microscopy over the course of 8 weeks. Our in vitro results demonstrate that RPESC suspension in a 0.2% HA solution promotes better initial cell distribution, proliferation, cobblestone formation, and expression of RPE cell markers (microphthalmiaassociated transcription factor and orthodenticle homeobox 2) after 96 hr of storage.These data suggest that HA addition to the vehicle can significantly enhance RPESC performance in vitro and is a promising strategy to pursue an improved delivery vehicle supporting in vivo RPE cell transplantation.

show abstract

Stem Cell-Based Therapy for Diseases of the Retinal Pigment Epithelium: From Bench to Bedside

Cited by 26 publications

References 40 publications

Volumetric Measurement of Subretinal Blebs Using Microscope-Integrated Optical Coherence Tomography

Volumetric Measurement of Subretinal Blebs Using Microscope-Integrated Optical Coherence Tomography

Manipulation of Panx1 Activity Increases the Engraftment of Transplanted Lacrimal Gland Epithelial Progenitor Cells

Screening and optimization of potential injection vehicles for storage of retinal pigment epithelial stem cell before transplantation

Contact Info

Product

Resources

About