Second-Harmonic Imaging Microscopy of Normal Human and Keratoconus Cornea

Morishige, Naoyuki; Wahlert, Andrew; Kenney, M. Cristina; Brown, Donald J.; Kawamoto, Koji; Chikama, Tai-ichiro; Nishida, Teruo; Jester, James V.

doi:10.1167/iovs.06-1177

Cited by 238 publications

(212 citation statements)

References 20 publications

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“…Although stromal thinning in KC has been attributed to collagen degradation by proteolytic enzymes 30,31 or decreased levels of proteinase inhibitors, 32 it has also been proposed that collagen is not lost but simply redistributed within the cornea by slippage between the lamellae. 33 This latter mechanism is supported by the observation of reduced inter-lamellar adhesion, 34 lamellar interlacing in the apex of KC corneas 35,36 and a reduced number of lamellar insertions into Bowman's layer. 35 X-ray diffraction studies provide some of the strongest evidence to support this theory.…”

Section: Biomechanicsmentioning

confidence: 80%

“…33 This latter mechanism is supported by the observation of reduced inter-lamellar adhesion, 34 lamellar interlacing in the apex of KC corneas 35,36 and a reduced number of lamellar insertions into Bowman's layer. 35 X-ray diffraction studies provide some of the strongest evidence to support this theory. In the deeper stromal layers of the healthy cornea the collagen is predominantly aligned in the superiorinferior and nasal-temporal orthogonal directions.…”

Section: Biomechanicsmentioning

confidence: 80%

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The pathogenesis of keratoconus

Davidson¹,

Hayes

Hardcastle³

et al. 2013

Eye

293

200

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Keratoconus (KC) is a common degenerative condition that frequently results in visual loss with an onset typically in early adulthood. It is the single most common reason for keratoplasty in the developed world. The cause and underlying pathological mechanism are unknown, but both environmental and genetic factors are thought to contribute to the development of the disease. Various strategies have been employed to address the gap in our understanding of this complex disease, with the expectation that over time more sophisticated therapies will be developed. In this review we summarise our current knowledge of the aetiology and risk factors associated with KC.

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Section: Biomechanicsmentioning

confidence: 80%

Section: Biomechanicsmentioning

confidence: 80%

The pathogenesis of keratoconus

Davidson¹,

Hayes

Hardcastle³

et al. 2013

Eye

293

200

View full text Add to dashboard Cite

show abstract

“…Tissue degradation alone does not account for that systematic realignment of fibrils, and so the authors suggested that both slippage and remodeling have a role. Morishige et al, 83 using second-harmonic imaging, identified less lamellar interweaving and a marked reduction or loss of lamellae inserting into Bowman's layer in corneas with keratoconus.…”

Section: Corneal Stroma Compositionmentioning

confidence: 99%

Keratoconus: an inflammatory disorder?

Galvis

Sherwin

Tello

et al. 2015

Eye

301

199

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Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition.

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“…Hence, to preserve vision, it is important to characterize two elements central to connective tissues, namely the orientation and organization of the collagen fibers that form them [5,6]. Several techniques have been developed for measuring collagen fiber orientation and organization, including small angle light scattering [7,8], x-ray scattering [9][10][11][12], non-linear microscopy [7,13,14] and magnetic resonance imaging [15,16], or for estimating them using inverse numerical methods [17,18]. The complexity of the eye calls for a technique that provides data at multiple scales, including high resolution (micron-scale) and broad field of view (several mm to cm) [19].…”

Section: Introductionmentioning

confidence: 99%

Polarization microscopy for characterizing fiber orientation of ocular tissues

Jan

Grimm

Tran

et al. 2015

Biomed. Opt. Express

150

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Characterizing the collagen fiber orientation and organization in the eye is necessary for a complete understanding of ocular biomechanics. In this study, we assess the performance of polarized light microscopy to determine collagen fiber orientation of ocular tissues. Our results demonstrate that the method provides objective, accurate, repeatable and robust data on fiber orientation with µm-scale resolution over a broad, cmscale, field of view, unaffected by formalin fixation, without requiring tissue dehydration, labeling or staining. Together, this shows that polarized light microscopy is a powerful method for studying collagen architecture in the eye, with applications ranging from normal physiology and aging, to pathology and transplantation.

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Second-Harmonic Imaging Microscopy of Normal Human and Keratoconus Cornea

Cited by 238 publications

References 20 publications

The pathogenesis of keratoconus

The pathogenesis of keratoconus

Keratoconus: an inflammatory disorder?

Polarization microscopy for characterizing fiber orientation of ocular tissues

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