Skip to main content

Advertisement

Log in

Persistent Epithelial Defects Due to Neurotrophic Keratopathy Treated with a Substance P-Derived Peptide and Insulin-Like Growth Factor 1

  • CLINICAL INVESTIGATION
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

The loss of corneal sensation results in the development of persistent corneal epithelial defects. The combination of a substance P-derived peptide, phenylalanine -glycine-leucine-methionine (FGLM)-amide, and insulin-like growth factor 1 (IGF-1) stimulates corneal epithelial migration in vitro and corneal epithelial wound closure in vivo. The clinical efficacy of eye drops containing FGLM-amide and IGF-1 for the treatment of persistent epithelial defects in individuals with neurotrophic keratopathy was examined in a prospective open study.

Methods

Eleven patients with persistent corneal epithelial defects associated with neurotrophic keratopathy were treated for up to 28 days by the administration of eye drops containing FGLM-amide and IGF-1. The course of epithelial healing was monitored by slit-lamp examination, and visual acuity was measured before and after treatment.

Results

Complete epithelial resurfacing was achieved in eight of the nine (89%) cases of persistent epithelial defects in the nine patients who received the full course of treatment. Epithelial defects had completely resurfaced in two of nine (22%) and five of nine (56%) cases within 1 and 2 weeks, respectively, after treatment initiation. No adverse effects of treatment were observed in any of the 11 patients.

Conclusions

Eye drops containing FGLM-amide and IGF-1 induced the rapid resurfacing of persistent epithelial defects in individuals with neurotrophic keratopathy. Jpn J Ophthalmol 2007;51:442–447 © Japanese Ophthalmological Society 2007

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. SD Klyce RW Beuerman (1997) Structure and function of the cornea HE Kaufman MB McDonald (Eds) The cornea EditionNumber2nd ed Butterworth-Heinemann Newton, MA 3–50

    Google Scholar 

  2. AJ Rozsa RW Beuerman (1982) ArticleTitleDensity and organization of free nerve endings in the corneal epithelium of the rabbit Pain 14 105–120 Occurrence Handle7177676 Occurrence Handle10.1016/0304-3959(82)90092-6 Occurrence Handle1:STN:280:BiyD1M%2Fgsl0%3D

    Article  PubMed  CAS  Google Scholar 

  3. EB Gross SuffixJr (1997) Corneal and external disease: clinical diagnosis and management JK Krachmer EJ Holland (Eds) Cornea, vol. 2. Neurotrophic keratitis Mosby Year Book St. Louis, MO 1339–1347

    Google Scholar 

  4. JJ Dutton (1999) Orbital anatomy and imaging: clinical anatomy of the orbit M Yanoff (Eds) Ophthalmology Mosby International London 7.2.1–7.2.8

    Google Scholar 

  5. M Nakamura T Chikama T Nishida (1998) ArticleTitleUp-regulation of integrin α5 expression by combination of substance P and insulin-like growth factor-1 in rabbit corneal epithelial cells Biochem Biophys Res Commun 246 777–782 Occurrence Handle9618288 Occurrence Handle10.1006/bbrc.1998.8704 Occurrence Handle1:CAS:528:DyaK1cXjsFGks7Y%3D

    Article  PubMed  CAS  Google Scholar 

  6. T Chikama M Nakamura T Nishida (1999) ArticleTitleUp-regulation of integrin α5 by a C-terminus four-amino-acid sequence of substance P (phenylalanine-glycine-leucine-methionine-amide) synergistically with insulin-like growth factor-1 in SV-40 transformed human corneal epithelial cells Biochem Biophys Res Commun 255 692–697 Occurrence Handle10049772 Occurrence Handle10.1006/bbrc.1999.0267 Occurrence Handle1:CAS:528:DyaK1MXhtlChsrk%3D

    Article  PubMed  CAS  Google Scholar 

  7. T Nishida M Nakamura K Ofuji et al. (1996) ArticleTitleSynergistic effects of substance P with insulin-like growth factor-1 on epithelial migration of the cornea J Cell Physiol 169 159–166 Occurrence Handle8841432 Occurrence Handle10.1002/(SICI)1097-4652(199610)169:1<159::AID-JCP16>3.0.CO;2-8 Occurrence Handle1:CAS:528:DyaK28XmtFClu7s%3D

    Article  PubMed  CAS  Google Scholar 

  8. M Nakamura K Ofuji T Chikama et al. (1997) ArticleTitleCombined effects of substance P and insulin-like growth factor-1 on corneal epithelial wound closure of rabbit in vivo Curr Eye Res 16 275–278 Occurrence Handle9088746 Occurrence Handle10.1076/ceyr.16.3.275.15409 Occurrence Handle1:STN:280:ByiB2czptVE%3D

    Article  PubMed  CAS  Google Scholar 

  9. K Ofuji M Nakamura T Nishida (2000) ArticleTitleSignaling regulation for synergistic effects of substance P and insulin-like growth factor-1 or epidermal growth factor on corneal epithelial migration Jpn J Ophthalmol 44 1–8 Occurrence Handle10698018 Occurrence Handle10.1016/S0021-5155(99)00168-9 Occurrence Handle1:CAS:528:DC%2BD3cXjtFSqtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  10. SM Brown DW Lamberts TW Reid et al. (1997) ArticleTitleNeurotrophic and anhidrotic keratopathy treated with substance P and insulin-like growth factor 1 Arch Ophthalmol 115 926–927 Occurrence Handle9230840 Occurrence Handle1:STN:280:ByiA2svjvFU%3D

    PubMed  CAS  Google Scholar 

  11. M Nakamura T Chikama T Nishida (1999) ArticleTitleSynergistic effect with Phe-Gly-Leu-Met-NH2 of the C-terminal of substance P and insulin-like growth factor-1 on epithelial wound healing of rabbit cornea Br J Pharmacol 127 489–497 Occurrence Handle10385250 Occurrence Handle10.1038/sj.bjp.0702550 Occurrence Handle1:CAS:528:DyaK1MXjs1yqsbo%3D

    Article  PubMed  CAS  Google Scholar 

  12. T Chikama K Fukuda N Morishige et al. (1998) ArticleTitleTreatment of neurotrophic keratopathy with substance-P-derived peptide (FGLM) and insulin-like growth factor I Lancet 351 1783–1784 Occurrence Handle9635953 Occurrence Handle10.1016/S0140-6736(98)24024-4 Occurrence Handle1:STN:280:DyaK1c3pslyktA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  13. R Kawamori (2002) ArticleTitleDiabetes trends in Japan Diabetes Metab Res Rev 18 IssueIDSuppl 3 S9–13 Occurrence Handle12324979 Occurrence Handle10.1002/dmrr.296

    Article  PubMed  Google Scholar 

  14. M Nakamura T Nagano T Chikama et al. (1998) ArticleTitleUp-regulation of phosphorylation of focal adhesion kinase and paxillin by combination of substance P and IGF-1 in SV-40 transformed human corneal epithelial cells Biochem Biophys Res Commun 242 16–20 Occurrence Handle9439602 Occurrence Handle10.1006/bbrc.1997.7899 Occurrence Handle1:CAS:528:DyaK1cXjtl2qug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  15. M Yamada M Ogata M Kawai et al. (2000) ArticleTitleDecreased substance P concentrations in tears from patients with corneal hypesthesia Am J Ophthalmol 129 671–672 Occurrence Handle10844065 Occurrence Handle10.1016/S0002-9394(00)00415-3 Occurrence Handle1:CAS:528:DC%2BD3cXkt1Cns7Y%3D

    Article  PubMed  CAS  Google Scholar 

  16. N Yamada R Yanai M Inui et al. (2005) ArticleTitleSensitizing effect of substance P on corneal epithelial migration induced by IGF-1, fibronectin, or interleukin-6 Invest Ophthalmol Vis Sci 46 833–839 Occurrence Handle15728538 Occurrence Handle10.1167/iovs.04-0775

    Article  PubMed  Google Scholar 

  17. N Yamada R Yanai K Kawamoto et al. (2006) ArticleTitlePromotion of corneal epithelial wound healing by a tetrapeptide (SSSR) derived from IGF-1 Invest Ophthalmol Vis Sci 47 3286–3292 Occurrence Handle16877393 Occurrence Handle10.1167/iovs.05-1205

    Article  PubMed  Google Scholar 

  18. A Lambiase P Rama S Bonini et al. (1998) ArticleTitleTopical treatment with nerve growth factor for corneal neurotrophic ulcers N Engl J Med 338 1174–1180 Occurrence Handle9554857 Occurrence Handle10.1056/NEJM199804233381702 Occurrence Handle1:CAS:528:DyaK1cXivVSqur0%3D

    Article  PubMed  CAS  Google Scholar 

  19. S Bonini A Lambiase P Rama et al. (2000) ArticleTitleTopical treatment with nerve growth factor for neurotrophic keratitis Ophthalmology 107 1347–1351 Occurrence Handle10889110 Occurrence Handle10.1016/S0161-6420(00)00163-9 Occurrence Handle1:STN:280:DC%2BD3czkvFKntQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Teruo Nishida.

About this article

Cite this article

Nishida, T., Chikama, Ti., Morishige, N. et al. Persistent Epithelial Defects Due to Neurotrophic Keratopathy Treated with a Substance P-Derived Peptide and Insulin-Like Growth Factor 1. Jpn J Ophthalmol 51, 442–447 (2007). https://doi.org/10.1007/s10384-007-0480-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10384-007-0480-z

Key words

Navigation