臨床眼科71巻4号

2017年04月発行

特集 第70回日本臨床眼科学会講演集［2］ 特別講演

臨床所見から考える網膜硝子体疾患の病態と治療

著者： 池田恒彦¹

所属機関： ¹大阪医科大学眼科学教室

ページ範囲：P.471 - P.489

日常臨床で感じる素朴な疑問を出発点とし，筆者らが過去に行ってきた網膜硝子体疾患に関する病態研究のうち，特発性黄斑円孔，特発性黄斑上膜，糖尿病網膜症，加齢黄斑変性，テルソン症候群の5疾患について述べた。本講演内容は，今後さらなる検討を要するが，いずれも新しい病態論であり，今後の網膜硝子体疾患における病態解明の糸口となる可能性がある。

参考文献

1）Machemer R, Buettner H, Norton EW et al：Vitrectomy：a pars plana approach. Trans Am Acad Ophthalmol Otolaryngol 75：813-820, 1971

2）Fujii GY, De Juan E Jr, Humayun MS et al：A new 25-gauge instrument system for transconjunctival sutureless vitrectomy. Ophthalmology 109：1807-1812, 2002

3）Kishi S, Hagimura N, Shimizu K：The role of the premacular liquefied pocket and premacular vitreous cortex in idiopathic macular hole development. Am J Ophthalmol 122：622-628, 1996

4）Michalewska Z, Michalewski J, Adelman RA et al：Inverted internal limiting membrane flap technique for large macular holes. Ophthalmology 117：2018-2025, 2010

5）Lorenz HP, Adzick NS：Scarless skin wound repair in the fetus. West J Med 159：350-355, 1993

6）Hu MS, Rennert RC, McArdle A et al：The role of stem cells during scarless skin wound healing. Adv Wound Care 3：304-314, 2014

7）Ehninger D, Kempermann G：Neurogenesis in the adult hippocampus. Cell Tissue Res 331：243-250, 2008

8）Zhao C, Deng W, Gage FH：Mechanisms and functional implications of adult neurogenesis. Cell. 132：645-660, 2008

9）Whitman MC, Greer CA：Adult neurogenesis and the olfactory system. Prog Neurobiol 89：162-175, 2009

10）Malatesta P, Appolloni I, Calzolari F：Radial glia and neural stem cells. Cell Tissue Res 331：165-178, 2008

11）Li L, Clevers H：Coexistence of quiescent and active adult stem cells in mammals. Science 327：542-545, 2010

12）Solanas G, Benitah SA：Regenerating the skin：a task for the heterogeneous stem cell pool and surrounding niche. Nat Rev Mol Cell Biol 14：737-748, 2013

13）Nombela-Arrieta C, Silberstein LE：The science behind the hypoxic niche of hematopoietic stem and progenitors. Hematology Am Soc Hematol Educ Program 2014：542-547, 2014

14）Tropepe V, Coles BL, Chiasson BJ et al：Retinal stem cells in the adult mammalian eye. Science 287：2032-2036, 2000

15）Bhatia B, Singhal S, Lawrence JM et al：Distribution of Müller stem cells within the neural retina：evidence for the existence of a ciliary margin-like zone in the adult human eye. Exp Eye Res 89：373-382, 2009

16）Ikeda T, Puro DG：Nerve growth factor：a mitogenic signal for retinal Müller glial cells. Brain Res 649：260-264, 1994

17）Ikeda T, Puro DG：Regulation of retinal glial cell proliferation by antiproliferative molecules. Exp Eye Res 60：435-443, 1995

18）Ikeda T, Waldbillig RJ, Puro DG：Truncation of IGF-I yields two mitogens for retinal Müller glial cells. Brain Res 686：87-92, 1995

19）Ikeda T, Homma Y, Nisida K et al：Expression of transforming growth factor-betas and their receptors by human retinal glial cells. Curr Eye Res 17：546-550, 1998

20）Oku H, Ikeda T, Honma Y et al：Gene expression of neurotrophins and their high-affinity Trk receptors in cultured human Müller cells. Ophthalmic Res 34：38-42, 2002

21）Kida T, Ikeda T, Nishimura M et al：Renin-angiotensin system in proliferative diabetic retinopathy and its gene expression in cultured human müller cells. Jpn J Ophthalmol 47：36-41, 2003

22）Fischer AJ, Reh TA：Müller glia are a potential source of neural regeneration in the postnatal chicken retina. Nat Neurosci 4：247-252, 2001

23）Ooto S, Akagi T, Kageyama R et al：Potential for neural regeneration after neurotoxic injury in the adult mammalian retina. Proc Natl Acad Sci 101：13654-13659, 2004

24）Sugiyama T, Katsumura K, Nakamura K et al：Effects of chymase on the macular region in monkeys and porcine muller cells：probable involvement of chymase in the onset of idiopathic macular holes. Ophthalmic Res 38：201-208, 2006

25）Shibata M, Ikeda T, Nakamura K et al：Expression Sites of Neural Stem Cell-Related Genes in the Monkey Retina. J Stem Cell Res Ther 2015, 5：12 doi.org/10.4172/2157-7633.1000319

26）Miyazaki M, Takai S：Local angiotensinⅡ-generating system in vascular tissues：the roles of chymase. Hypertens Res 24：189-193, 2001

27）May CA：Mast cell heterogeneity in the human uvea. Histochem Cell Biol 112：381-386, 1999

28）Johnson JL, Jackson CL, Angelini GD et al：Activation of matrix-degrading metalloproteinases by mast cell proteases in atherosclerotic plaques. Arterioscler Thromb Vasc Biol 18：1707-1715, 1998

29）Boesiger J, Tsai M, Maurer M et al：Mast cells can secrete vascular permeability factor/vascular endothelial cell growth factor and exhibit enhanced release after immunoglobulin E-dependent upregulation of fc epsilon receptor I expression. J Exp Med 188：1135-1145, 1998

30）Levi-Schaffer F, Piliponsky AM：Tryptase, a novel link between allergic inflammation and fibrosis. Trends Immunol 24：158-161, 2003

31）Maruichi M, Oku H, Takai S et al：Measurement of activities in two different angiotensinⅡ generating systems, chymase and angiotensin-converting enzyme, in the vitreous fluid of vitreoretinal diseases：a possible involvement of chymase in the pathogenesis of macular hole patients. Curr Eye Res 29：321-325, 2004

32）Nguyen M, Pace AJ, Koller BH：Age-induced reprogramming of mast cell degranulation. J Immunol 175：5701-5707, 2005

33）Yamashita T, Yamashita T, Kawano H et al：Early imaging of macular hole closure：a diagnostic technique and its quality for gas-filled eyes with spectral domain optical coherence tomography. Ophthalmologica 229：43-49, 2013

34）Codega P, Silva-Vargas V, Paul A et al：Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche. Neuron 82：545-559, 2014

35）Kishi S, Shimizu K：Oval defect in detached posterior hyaloid membrane in idiopathic preretinal macular fibrosis. Am J Ophthalmol 118：451-456, 1994

36）Foos RY：Vitreoretinal juncture；epiretinal membranes and vitreous. Invest Ophthalmol Vis Sci 16：416-422, 1977

37）Charteris DG, Hiscott P, Grierson I et al：Proliferative vitreoretinopathy. Lymphocytes in epiretinal membranes. Ophthalmology 99：1364-1347, 1992

38）Yu J, Feng L, Wu Y et al：Vitreous proteomic analysis of idiopathic epiretinal membranes. Mol Biosyst 10：2558-2566, 2014

39）Pollreisz A, Funk M, Breitwieser FP et al：Quantitative proteomics of aqueous and vitreous fluid from patients with idiopathic epiretinal membranes. Exp Eye Res 108：48-58, 2013

40）Ikeda T, Nakamura K, Oku H et al：The role of tryptase and anti-type Ⅱ collagen antibodies in the pathogenesis of idiopathic epiretinal membranes. Clin Ophthalmol 9：1181-1186, 2015

41）Cairns JA：Inhibitors of mast cell tryptase beta as therapeutics for the treatment of asthma and inflammatory disorders. Pulm Pharmacol Ther 18：55-66, 2005

42）Yamamoto K, Kumagai N, Fukuda K et al：Activation of corneal fibroblast-derived matrix metalloproteinase-2 by tryptase. Curr Eye Res 31：313-317, 2006

43）Sendo T, Sumimura T, Itoh Y et al：Involvement of proteinase-activated receptor-2 in mast cell tryptase-induced barrier dysfunction in bovine aortic endothelial cells. Cell Signal 15：773-781, 2003

44）Kojima S, Sugiyama T, Takai S et al：Effects of gelatin hydrogel containing chymase inhibitor on scarring in a canine filtration surgery model. Invest Ophthalmol Vis Sci 52：7672-7680, 2011

45）Lewis H, Abrams GW, Blumenkranz MS et al：Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. Ophthalmology 99：753-759, 1992

46）Tachi N, Ogino N：Vitrectomy for diffuse macular edema in cases of diabetic retinopathy. Am J Ophthalmol 122：258-260, 1996

47）McLeod DS, Lefer DJ, Merges C et al：Enhanced expression of intracellular adhesion molecule-1 and P-selectin in the diabetic human retina and choroid. Am J Pathol 147：642-653, 1995

48）Lutty GA, Cao J, McLeod DS：Relationship of polymorphonuclear leukocytes to capillary dropout in the human diabetic choroid. Am J Pathol 151：707-714, 1997

49）Miyamoto K, Hiroshiba N, Tsujikawa A et al：In vivo demonstration of increased leukocyte entrapment in retinal microcirculation of diabetic rats. Invest Ophthalmol Vis Sci 39：2190-2194, 1998

50）Satofuka S, Ichihara A, Nagai N et al：（Pro）renin receptor-mediated signal transduction and tissue renin-angiotensin system contribute to diabetes-induced retinal inflammation. Diabetes 58：1625-1633, 2009

51）Awa WL, Boehm BO, Rosinger S et al：HLA-typing, clinical, and immunological characterization of youth with type 2 diabetes mellitus phenotype from the German/Austrian DPV database. Pediatr Diabetes 14：562-574, 2013

52）Nayak RC, Agardh CD, Kwok MG et al：Circulating anti-pericyte autoantibodies are present in Type 2 diabetic patients and are associated with non-proliferative retinopathy. Diabetologia 46：511-513, 2003

53）Dugel PU, Blumenkranz MS, Haller JA et al：A randomized, dose-escalation study of subconjunctival and intravitreal injections of sirolimus in patients with diabetic macular edema. Ophthalmology 119：124-131, 2012

54）Terato K, Shimozuru Y, Katayama K et al：Specificity of antibodies to type Ⅱ collagen in rheumatoid arthritis. Arthritis Rheum 33：1493-1500, 1990

55）Balashova LM, ZaĬtseva NS, Teplinskaia LE et al：Antibodies to types Ⅱ and Ⅳ collagens, tumor necrosis factor-alpha and circulating immune complexes in lacrimal fluid and serum of patients with diabetic retinopathy and different stages. Vestn Oftalmol 116：31-34, 2000

56）Nakaizumi A, Fukumoto M, Kida T et al：Measurement of serum and vitreous concentrations of anti-type Ⅱcollagen antibody in diabetic retinopathy. Clin Ophthalmol 9：543-547, 2015

57）Yoo TJ, Stuart JM, Kang AH et al：Type Ⅱ collagen autoimmunity in otosclerosis and Meniere's Disease. Science 217：1153-1155, 1982

58）Levick JR：Permeability of rheumatoid and normal human synovium to specific plasma proteins. Arthritis Rheum 24：1550-1560, 1981

59）Juhn SK, Hunter BA, Odland RM：Blood-labyrinth barrier and fluid dynamics of the inner ear. Int Tinnitus J 7：72-83, 2001

60）Streilein JW：Immunological non-responsiveness and acquisition of tolerance in relation to immune privilege in the eye. Eye（Lond） 9：236-240, 1995

61）Vijayagopal P, Srinivasan SR, Radhakrishnamurthy B et al：Lipoprotein-proteoglycan complexes from atherosclerotic lesions promote cholesteryl ester accumulation in human monocytes/macrophages. Arterioscler Thromb 12：237-249, 1992

62）Grinspan JB, Stern JL, Franceschini B et al：Trophic effects of basic fibroblast growth factor（bFGF）on differentiated oligodendroglia：a mechanism for regeneration of the oligodendroglial lineage. J Neurosci Res 36：672-680, 1993

63）池田恒彦：硝子体の病態生理〜網膜硝子体疾患の分子レベルにおける病態解明．日眼会誌107：785-812，2003

64）Hosoki A, Oku H, Horie T et al：Changes in expression of nestin, CD44, vascular endothelial growth factor, and glutamine synthetase by mature Müller cells after dedifferentiation. J Ocul Pharmacol Ther 31：476-481, 2015

65）Paques M, Massin P, Gaudric A：Growth factors and diabetic retinopathy. Diabetes Metab 23：125-130, 1997

66）Sato N, Kohi S, Hirata K et al：Role of hyaluronan in pancreatic cancer biology and therapy：Once again in the spotlight. Cancer Sci 107：569-575, 2016

67）Ikeda T, Sawa H, Koizumi K et al：Pars plana vitrectomy for regression of choroidal neovascularization with age-related macular degeneration. Acta Ophthalmol Scand 78：460-464, 2000

68）Krebs I, Brannath W, Glittenberg C et al：Posterior vitreomacular adhesion：a potential risk factor for exudative age-related macular degeneration? Am J Ophthalmol 144：741-746, 2007

69）Lee SJ, Lee CS, Koh HJ：Posterior vitreomacular adhesion and risk of exudative age-related macular degeneration：paired eye study. Am J Ophthalmol 147：621-626, 2009

70）Roller AB, Mahajan VB, Boldt HC et al：Effects of vitrectomy on age-related macular degeneration. Ophthalmology 117：1381-1386, 2010

71）Sakamoto T, Sheu SJ, Arimura N et al：Vitrectomy for exudative age-related macular degeneration with vitreous hemorrhage. Retina 30：856-864, 2010

72）Suzuma I, Suzuma K, Ueki K et al：Stretch-induced retinal vascular endothelial growth factor expression is mediated by phosphatidylinositol 3-kinase and protein kinase C（PKC）-zeta but not by stretch-induced ERK1/2, Akt, Ras, or classical/novel PKC pathways. J Biol Chem 277：1047-1057, 2002

73）Groschner K：Two ways to feel the pressure：an endothelial Ca（2＋）entry channel with dual mechanosensitivity. Cardiovasc Res 53：9-11, 2002

74）Liu YL, Lin CP, Yang CM：Transient regression of choroidal neovascularization membrane after vitrectomy in age-related macular degeneration with vitreomacular traction syndrome. Acta Ophthalmol 89：e291-293, 2011

75）Kimura S, Morizane Y, Toshima S et al：Efficacy of vitrectomy and inner limiting membrane peeling in age-related macular degeneration resistant to anti-vascular endothelial growth factor therapy, with vitreomacular traction or epiretinal membrane. Graefes Arch Clin Exp Ophthalmol 254：1731-1736, 2016

76）Manschot WA：Subarachnoid hemorrhage；intraocular symptoms and their pathogenesis. Am J Ophthalmol 38：501-505, 1954

77）Hedges TR Jr, Walsh FB：Optic nerve sheath and subhyaloid hemorrhage as a complication of angiocardiography. AMA Arch Ophthalmol 54：425-427, 1955

78）佐藤孝樹・植木麻理・坂本理之・他：テルソン症候群における硝子体出血の発生機序に関する検討．眼紀56：813-816，2005

79）Sakamoto M, Nakamura K, Shibata M et al：Magnetic resonance imaging findings of Terson's syndrome suggesting a possible vitreous hemorrhage mechanism. Jpn J Ophthalmol 54：135-139, 2010

80）Esiri MM, Gay D：Immunological and neuropathological significance of the Virchow-Robin space. J Neurol Sci 100：3-8, 1990

81）Gärtner J：Importance of the perivascular space of the central vessels in vitreo-papillar drainage. Electrommicroscopie observations on the normal mouse eye and on the human eye under pathological conditions. Albrecht Von Graefes Arch Klin Exp Ophthalmol 175：13-27, 1968