Heterogeneity of cultured melanocyte elongation and proliferation factor in bilateral diffuse uveal melanocytic proliferation

Jeremy A. Lavine; Michael S. Ramos; Alyson M. Wolk; Kimberly Baynes; Sumit Sharma; Aleksandra V. Rachitskaya; Bela Anand-Apte; Sunil K. Srivastava; Alex Yuan

doi:10.1016/j.exer.2019.04.006

Heterogeneity of cultured melanocyte elongation and proliferation factor in bilateral diffuse uveal melanocytic proliferation

Jeremy A. Lavine, Michael S. Ramos, Alyson M. Wolk, Kimberly Baynes, Sumit Sharma, Aleksandra V. Rachitskaya, Bela Anand-Apte, Sunil K. Srivastava, Alex Yuan^*

^*Corresponding author for this work

Ophthalmology

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

A patient with bilateral diffuse uveal melanocytic proliferation (BDUMP) associated with endometrial cancer was treated with plasmapheresis, but failed therapy with progressive serous retinal detachment. We collected plasma before and after plasmapheresis therapy. Our goal was to determine if the cultured melanocyte elongation and proliferation (CMEP) factor and hepatocyte growth factor (HGF) was present in the IgG enriched fraction and understand why our patient failed plasmapheresis therapy. Melanocytes were cultured for 3–5 days in the presence of control medium, unfractionated pre-plasmapheresis BDUMP medium, IgG enriched or IgG depleted BDUMP medium, or unfractionated post-plasmapheresis BDUMP medium. Subretinal fluid was collected from patients with BDUMP and control retinal detachments and analyzed by electropheresis with immunoblotting. Medium with unfractionated BDUMP plasma stimulated melanocyte growth 1.4–1.5 fold compared to control medium on days 3–5 (p < 0.001 for all). Both IgG enriched and IgG depleted BDUMP medium mildly increased melanocyte growth 1.3 fold (p < 0.05 for enriched, p < 0.01 for depleted) compared to control. In comparison, unfractionated BDUMP medium caused a 1.7-fold increase in melanocyte growth, which was significantly more than the enriched (p < 0.01) and depleted (p < 0.05) fractions. Pre-plasmapheresis and post-plasmapheresis unfractionated BDUMP medium equally stimulated melanocyte growth 1.7-fold (p < 0.05) compared to control. HGF was present in IgG depleted, pre-plasmapheresis, and post-plasmapheresis samples, but absent in the IgG enriched fraction. There was no enrichment of IgG in the subretinal fluid from eyes with BDUMP. In conclusion, CMEP factor is not concentrated in the IgG enriched plasma fraction in our patient who failed plasmapheresis therapy. HGF levels have no correlation with melanocyte growth. Because plasmapheresis preferentially removes immunoglobulins from the plasma, our patient responded poorly to plasmapheresis treatment with worsening retinal detachment.

Original language	English (US)
Pages (from-to)	30-37
Number of pages	8
Journal	Experimental eye research
Volume	184
DOIs	https://doi.org/10.1016/j.exer.2019.04.006
State	Published - Jul 2019

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. We thank Dr. Jerome Schartman of Retina Associates of Cleveland for the images from the patient's initial presentation, which are presented in Fig. 1. SKS receives research support from Allergan (Dublin, Ireland), Santen (Osaka, Japan), and Psivida (Watertown, MA). BAA is supported by RO1EY027083, R01EY026181, R01EY015638, and P30EY025585, a Research to Prevent Blindness Challenge Grant. AY is supported by National Eye Institute K08EY023608. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. We thank Dr. Jerome Schartman of Retina Associates of Cleveland for the images from the patient's initial presentation, which are presented in Fig. 1 . SKS receives research support from Allergan (Dublin, Ireland) , Santen (Osaka, Japan) , and Psivida (Watertown, MA) . BAA is supported by RO1EY027083 , R01EY026181 , R01EY015638 , and P30EY025585 , a Research to Prevent Blindness Challenge Grant. AY is supported by National Eye Institute K08EY023608 .

Keywords

Bilateral diffuse uveal melanocytic proliferation (BDUMP)
Cultured melanocyte elongation and proliferation factor (CMEP)
Hepatocyte growth factor (HGF)
IgG
Melanocyte
Plasmapheresis
Serous retinal detachment (SRD)

ASJC Scopus subject areas

Ophthalmology
Sensory Systems
Cellular and Molecular Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.exer.2019.04.006

Cite this

@article{49dc5969958547938e0d1de69c306e37,

title = "Heterogeneity of cultured melanocyte elongation and proliferation factor in bilateral diffuse uveal melanocytic proliferation",

abstract = "A patient with bilateral diffuse uveal melanocytic proliferation (BDUMP) associated with endometrial cancer was treated with plasmapheresis, but failed therapy with progressive serous retinal detachment. We collected plasma before and after plasmapheresis therapy. Our goal was to determine if the cultured melanocyte elongation and proliferation (CMEP) factor and hepatocyte growth factor (HGF) was present in the IgG enriched fraction and understand why our patient failed plasmapheresis therapy. Melanocytes were cultured for 3–5 days in the presence of control medium, unfractionated pre-plasmapheresis BDUMP medium, IgG enriched or IgG depleted BDUMP medium, or unfractionated post-plasmapheresis BDUMP medium. Subretinal fluid was collected from patients with BDUMP and control retinal detachments and analyzed by electropheresis with immunoblotting. Medium with unfractionated BDUMP plasma stimulated melanocyte growth 1.4–1.5 fold compared to control medium on days 3–5 (p < 0.001 for all). Both IgG enriched and IgG depleted BDUMP medium mildly increased melanocyte growth 1.3 fold (p < 0.05 for enriched, p < 0.01 for depleted) compared to control. In comparison, unfractionated BDUMP medium caused a 1.7-fold increase in melanocyte growth, which was significantly more than the enriched (p < 0.01) and depleted (p < 0.05) fractions. Pre-plasmapheresis and post-plasmapheresis unfractionated BDUMP medium equally stimulated melanocyte growth 1.7-fold (p < 0.05) compared to control. HGF was present in IgG depleted, pre-plasmapheresis, and post-plasmapheresis samples, but absent in the IgG enriched fraction. There was no enrichment of IgG in the subretinal fluid from eyes with BDUMP. In conclusion, CMEP factor is not concentrated in the IgG enriched plasma fraction in our patient who failed plasmapheresis therapy. HGF levels have no correlation with melanocyte growth. Because plasmapheresis preferentially removes immunoglobulins from the plasma, our patient responded poorly to plasmapheresis treatment with worsening retinal detachment.",

keywords = "Bilateral diffuse uveal melanocytic proliferation (BDUMP), Cultured melanocyte elongation and proliferation factor (CMEP), Hepatocyte growth factor (HGF), IgG, Melanocyte, Plasmapheresis, Serous retinal detachment (SRD)",

author = "Lavine, {Jeremy A.} and Ramos, {Michael S.} and Wolk, {Alyson M.} and Kimberly Baynes and Sumit Sharma and Rachitskaya, {Aleksandra V.} and Bela Anand-Apte and Srivastava, {Sunil K.} and Alex Yuan",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

year = "2019",

month = jul,

doi = "10.1016/j.exer.2019.04.006",

language = "English (US)",

volume = "184",

pages = "30--37",

journal = "Experimental eye research",

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T1 - Heterogeneity of cultured melanocyte elongation and proliferation factor in bilateral diffuse uveal melanocytic proliferation

AU - Lavine, Jeremy A.

AU - Ramos, Michael S.

AU - Wolk, Alyson M.

AU - Baynes, Kimberly

AU - Sharma, Sumit

AU - Rachitskaya, Aleksandra V.

AU - Anand-Apte, Bela

AU - Srivastava, Sunil K.

AU - Yuan, Alex

PY - 2019/7

Y1 - 2019/7

N2 - A patient with bilateral diffuse uveal melanocytic proliferation (BDUMP) associated with endometrial cancer was treated with plasmapheresis, but failed therapy with progressive serous retinal detachment. We collected plasma before and after plasmapheresis therapy. Our goal was to determine if the cultured melanocyte elongation and proliferation (CMEP) factor and hepatocyte growth factor (HGF) was present in the IgG enriched fraction and understand why our patient failed plasmapheresis therapy. Melanocytes were cultured for 3–5 days in the presence of control medium, unfractionated pre-plasmapheresis BDUMP medium, IgG enriched or IgG depleted BDUMP medium, or unfractionated post-plasmapheresis BDUMP medium. Subretinal fluid was collected from patients with BDUMP and control retinal detachments and analyzed by electropheresis with immunoblotting. Medium with unfractionated BDUMP plasma stimulated melanocyte growth 1.4–1.5 fold compared to control medium on days 3–5 (p < 0.001 for all). Both IgG enriched and IgG depleted BDUMP medium mildly increased melanocyte growth 1.3 fold (p < 0.05 for enriched, p < 0.01 for depleted) compared to control. In comparison, unfractionated BDUMP medium caused a 1.7-fold increase in melanocyte growth, which was significantly more than the enriched (p < 0.01) and depleted (p < 0.05) fractions. Pre-plasmapheresis and post-plasmapheresis unfractionated BDUMP medium equally stimulated melanocyte growth 1.7-fold (p < 0.05) compared to control. HGF was present in IgG depleted, pre-plasmapheresis, and post-plasmapheresis samples, but absent in the IgG enriched fraction. There was no enrichment of IgG in the subretinal fluid from eyes with BDUMP. In conclusion, CMEP factor is not concentrated in the IgG enriched plasma fraction in our patient who failed plasmapheresis therapy. HGF levels have no correlation with melanocyte growth. Because plasmapheresis preferentially removes immunoglobulins from the plasma, our patient responded poorly to plasmapheresis treatment with worsening retinal detachment.

AB - A patient with bilateral diffuse uveal melanocytic proliferation (BDUMP) associated with endometrial cancer was treated with plasmapheresis, but failed therapy with progressive serous retinal detachment. We collected plasma before and after plasmapheresis therapy. Our goal was to determine if the cultured melanocyte elongation and proliferation (CMEP) factor and hepatocyte growth factor (HGF) was present in the IgG enriched fraction and understand why our patient failed plasmapheresis therapy. Melanocytes were cultured for 3–5 days in the presence of control medium, unfractionated pre-plasmapheresis BDUMP medium, IgG enriched or IgG depleted BDUMP medium, or unfractionated post-plasmapheresis BDUMP medium. Subretinal fluid was collected from patients with BDUMP and control retinal detachments and analyzed by electropheresis with immunoblotting. Medium with unfractionated BDUMP plasma stimulated melanocyte growth 1.4–1.5 fold compared to control medium on days 3–5 (p < 0.001 for all). Both IgG enriched and IgG depleted BDUMP medium mildly increased melanocyte growth 1.3 fold (p < 0.05 for enriched, p < 0.01 for depleted) compared to control. In comparison, unfractionated BDUMP medium caused a 1.7-fold increase in melanocyte growth, which was significantly more than the enriched (p < 0.01) and depleted (p < 0.05) fractions. Pre-plasmapheresis and post-plasmapheresis unfractionated BDUMP medium equally stimulated melanocyte growth 1.7-fold (p < 0.05) compared to control. HGF was present in IgG depleted, pre-plasmapheresis, and post-plasmapheresis samples, but absent in the IgG enriched fraction. There was no enrichment of IgG in the subretinal fluid from eyes with BDUMP. In conclusion, CMEP factor is not concentrated in the IgG enriched plasma fraction in our patient who failed plasmapheresis therapy. HGF levels have no correlation with melanocyte growth. Because plasmapheresis preferentially removes immunoglobulins from the plasma, our patient responded poorly to plasmapheresis treatment with worsening retinal detachment.

KW - Bilateral diffuse uveal melanocytic proliferation (BDUMP)

KW - Cultured melanocyte elongation and proliferation factor (CMEP)

KW - Hepatocyte growth factor (HGF)

KW - IgG

KW - Melanocyte

KW - Plasmapheresis

KW - Serous retinal detachment (SRD)

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Heterogeneity of cultured melanocyte elongation and proliferation factor in bilateral diffuse uveal melanocytic proliferation

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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Data for: Heterogeneity of Cultured Melanocyte Elongation and Proliferation Factor in Bilateral Diffuse Uveal Melanocytic Proliferation

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Heterogeneity of cultured melanocyte elongation and proliferation factor in bilateral diffuse uveal melanocytic proliferation

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Datasets

Data for: Heterogeneity of Cultured Melanocyte Elongation and Proliferation Factor in Bilateral Diffuse Uveal Melanocytic Proliferation

Cite this