Retina en felinos

Enfermedades de la retina Felina

11째 Simposio Platense de Medicina Veterinaria

Pablo Sande, MV, PhD, DCLOVE p_sande@yahoo.com www.veteoftalmo.com.ar

Esquema de la retina

Inflamaci贸n

Vasos Coroideos

Atrofia

Vasos Retinianos

Normal

Retina Normal

Examen del fondo del ojo

Directo

Indirecto

Panoptico

ERG

Métodos complementarios

Mixto Conos

Pot. Osc.

! Guidelines for clinical electroretinography in the dog KRISTINA NARFSTRÖM1, BJÖRN EKESTEN2, SERGE G. ROSOLEN3,B ERNHARD M. SPIESS4, CHRISTINE L. PERCICOT5 and RON OFRI6, Documenta Ophthalmologica 105: 83–92, 2002.

RFG

MĂŠtodos complementarios

贸g Ec

ERG

Or 谩c ul o

RFG

o raf

Hereditarias Nutricionales Vasculares Inflamatorias T贸xicas

Degeneraciones Hereditarias, Atrofia progresiva de la Retina

# Ceguera progresiva, primero nocturna, luego diurna, desde periferia al centro

! - - - - - - - - - - - - - - - - - - - - - -

! APR esta probada en el Gato Abisinio

! Barnett y Carlise la describieron en siameses

! Rubin y Lipton la describieron en Persas

! Buyukmichi en gatos mestizos

Functional Assessment of the Regional Distribution of Disease in a Cat Model of Hereditary Retinal Degeneration Mathias W. Seeliger1 and Kristina NarfstroÂ¨m2

Atrofia progresiva de la Retina, Electrorretinografia

Nutricionales, Deficiencia de Taurina

# Amino谩cido esencial en los felinos

! # 10mg/kg de requerimiento diario

! # Mayor concentraci贸n en retina y coraz贸n

! # Incluidos en los A. Balanceados

Imรกgenes angiograficas

Electrorretinografia

F. Blanco

F. Azul

Â Â Flicker

Pot. Oscilatorios

Nutricionales, Deficiencia de Taurina

# Las lesiones reflejadas en el ERG comienzan a las 10 semanas

! # Las lesiones oftalmoscopicas comienzan entre los 3 y 7 meses ! # La ceguera completa se hace evidente 9 a 10 meses

Vasculares, Retinopatia Hipertensiva La hipertensión sistémica :

! 1. Primaria

! 2. Secundaria #Insuficiencia renal

! # Hipertiroidismo

! # Patologías cardiacas

! # Diabetes mellitus

! # Anemias prolongadas

Sistólica:

160mmhg

Diastólica: 100mmhg Ocular lesions associated with systemic hypertension in cats: 69 cases (1985-1998). Maggio F, DeFrancesco TC, Atkins CE, Pizzirani S, Gilger BC, Davidson MG. J Am Vet Med Assoc. 2000 Sep 1;217(5):695-702. Clinica Veterinaria Europa, Florence, Italy.

Vasculares, Retinopatia Hipertensiva

Prevalencia de lesiones retinianas en gatos con hipertensión: 48% !

262 +/- 34 mmhg

con retinopatía !

221 +/- 34 mmhg

sin retinopatía

Hypertensive retinopathy and choroidopathy in a cat. Komáromy AM, Andrew SE, Denis HM, Brooks DE, Gelatt KN. Vet Ophthalmol. 2004 Jan-Feb;7(1):3-9. Spontaneous feline hypertension: clinical and echocardiographic abnormalities, and survival rate. Chetboul V, Lefebvre HP, Pinhas C, Clerc B, Boussouf M, Pouchelon JL. J Vet Intern Med. 2003 Jan-Feb; 17(1):89-95.

Imagenes angiograficas

Vasculares, Retinopatia Hipertensiva

# Daño vascular con perdida de plasma y células

! # Hemorragias en retina y vítreo, desprendimientos de retina

! # Droga de elección: Amlodipina 0.625 a 1,25mg día

Signos en el Segmento Anterior

â&#x20AC;&#x153;Reconocer a los gatos en riesgo es importante a la hora de conservar la visiĂłnâ&#x20AC;?

Inflamatorias, coroideoretinitis

# Focales # Difusas # Multifocales

Barrera Hemato-retiniana

BHO (Interna)

BHO (Externa)

SMI-32 (

SMI-32 / DAPI

1 0.5 0 Inflamatorias, coroideoretinitis Cx3cr1 Cx3cr1 GFP/+

Fib +/+

Healthy

Pre-onset EAE

Peak EAE

GFP/+

Fib!390-396Α

Figure

Fibrinogen

perivascular

microglial

m e d i at e s

clustering

and

axonal damage via CD11b/CD18 (b)

ARTICLE

NATURE COMMUNICATIONS | DOI: 10.1038/ncomms2230

Schematic

mo del

illustration

the

Peak EAE Cx3cr1GFP/+Fib!390-396A

Cx3cr1GFP/+ / Rhodamine dextran

Cx3cr1GFP/+Fib +/+

SMI-32 (% area)

SMI-32 / DAPI

Pial macrophage

co nt r i b u t i o n

stochastically

Cx3cr1GFP/+ Cx3cr1GFP/+ Fib +/+ Fib!390-396Α

Pre-onset EAE

and

p i al

a xo n al

d am ag e

extend

and

retract

their

processes. In EAE mice before the onset

neuro logical

symptoms

fibrinogen

leaks in the CNS, triggering microglial

1.5

proce ss

1 0.5

exte nsio n

and

cell

body

accumulation toward the vasculature. At the peak of disease, microglial clustering

Cx3cr1GFP/+ Cx3cr1GFP/+ Fib!390-396Α Fib +/+

around Healthy

microg lia

CNS, microglia are evenly distributed and

responses

neuroinflammatory disease. In the healthy

20 0

dynamic

working

macrophages to BBB disruption and their

2.5

Microglia b

Clusters per 0.5 mm3

p e r i va s c u lar

and

Peak EAE

the

vasculature

occurs

almost

exclusively in areas of fibrin deposition and is associated with axonal damage

Fibrinogen

and

ROS

r e le a s e

ROS

m icro g lia.

Fibrinogen signaling via the CD11b/CD18

Axon

integrin

Basal membrane

formation of

receptor

required

for

the

perivascular clusters and

the development of axonal damage.

ogen mediates perivascular microglial clustering and axonal damage via CD11b/CD18. (a) In vivo imaging of Cx3cr1GFP/ þ Fibg390-396A Microglia NATURE COMMUNICATIONS Pial macrophage of EAE (n ¼ 6) shows fewer perivascular clusters (top) and significantly less SMI-32 immunoreactivity (bottom) than in Cx3cr1GFP/ þ Fibrinogen ROS (n ¼ 9). Correlated histology was performed in the same spinal cord areas in the mice that were previously imaged in vivo. Values are # Fibrinogen-induced perivascular microglial clustering is required for the development of Axon o0.05 (Mann–Whitney test). Scale Basal bars, top: 10 mm; bottom: 50 mm. (b) Schematic illustration and working model of the dynamic membrane axonal damage in neuroinflammation vascular microglia and pial macrophages to BBB disruption and their contribution to axonal damage in neuroinflammatory disease. In the Figure 8 | Fibrinogen mediates perivascular microglial clustering and axonal damage via CD11b/CD18. (a) In vivo imaging of Cx3cr1 Fib mice at the peak of EAE (n ¼ 6) shows fewer perivascular clusters (top) and significantly less SMI-32 immunoreactivity (bottom) than in Cx3cr1 roglia are evenly distributed and stochastically extend and retract processes. In EAE mice Fib controls (n ¼ 9). Correlated histology was performed in the same spinal cord areas intheir the mice that were previously imaged in vivo. Values are before the onset of neurological symptoms mean±s.e.m. *Po0.05 (Mann–Whitney test). Scale bars, top: 10 mm; bottom: 50 mm. (b) Schematic illustration and working model of the dynamic 1 1 1 1 1,2, Thomas J. Deerinck3,4, Dimitri S. Dimitrios Davalos , Jae Kyu Ryu , Mario Merlini , accumulation Kim M. Baeten , Natacha , Mark Petersen n the CNS, triggering microglial process extension cell body toward the Invasculature. At1,w the peak ofA.disease, microglial responses of perivascular microglia and pial macrophages to BBB and disruption and their contribution to axonal damage in neuroinflammatory disease. the Le Moan healthy CNS, microglia are evenly distributed and stochastically extend and retract their processes. In EAE mice before the onset of neurological symptoms 1, Hiroyuki 4toward 1, Jennie d the vasculature almost exclusively in areas ofHakozaki deposition and is associated with axonal damage release of ROS 5by leaks in the CNS, triggering microglial process extension and cellfibrin body accumulation the vasculature. At the peak ofMurray disease, microglial Smirnoff1occurs , fibrinogen Catherine Bedard , Sara Gonias B. Ling1and , Hans Lassmann , Jay L. Degen6, Mark H. clustering around the vasculature occurs almost exclusively in areas of fibrin deposition and is associated with axonal damage and release of ROS by gen signaling via3,4 themicroglia. CD11b/CD18 integrin receptor required for ofthe formation perivascular clusters and the development of axonal Fibrinogen signaling via the CD11b/CD18 integrin receptor is required for the formation perivascular clusters and theof development of axonal 1,7 is GFP/ þ

þ/þ

Ellisman

& Katerina Akassoglou

damage.

g390-396A GFP/ þ

Causas mas frecuentes de Coriorretinitis

1. Infecciosas (Virales)

n u !! s ! o o c m Vi toco p i Cr

2. Micosis

PIF ViLeF ViF

3. Traumatismos !

4. Neoplasias

! o r Ra

5. Parasitaria

Toxoplasmosis

Inflamatorias, Toxoplasmosis

Toxoplasma gondii (for a review, see Dubey, 2004). )

Inflamatorias, Criptococosis

# Uveitis granulomatosa # Desprendimiento de retina # Neuritis optica Cryptococcus neoformans or Cryptococcus gattii (previously C. neoformans var gattii) (Wolf, 1989).

Inflamatorias, PIF

Inflamatorias, VIF

Inflamatorias, ViLeF

Toxicas, Secundarias a Quinolonas y algo mas……

Factores de Riesgo:

# Edad del paciente !

# Renopatías , hepatopatías !

# Dosis, duración y vías de administración

Retinal toxicity of liposome-incorporated and free ofloxacin after intravitreal injection in rabbit eyes.

Wiechens B, Neumann D, Grammer JB, Pleyer U, Hedderich J, Duncker GI. Int Ophthalmol. 1998-1999;22(3):133-43.

Fluoroquinolone-induced retinal degeneration in cats.

Wiebe V, Hamilton P. J Am Vet Med Assoc. 2002 Dec 1;221(11):1568-71. Review

Quinolonas, Características Histopatólogicas

# Vacuolas citoplasmáticas !

# Degeneración primaria de los conos !

# Edema !

# en la fase crónica hay deg en eración co mpleta de lo s fotorreceptores

Quinolonas, Bases genéticas

# Alteración de la proteína ABCG2 de la Barrera HematoOcular !

# Acumulación de la Quinolona en la retina !

# Formación de ROS y Daño retiniano

(Ramirez et al., 2011)

ElectrorretinografĂa

Tóxicas, Secundarias a Quinolonas y algo mas……

# Griseofulvina Degeneración súbita de fotorreceptores, supresión de la medula ósea y muerte (Rottman et al., 1991)

# Ivermectina #

signos

neurológicos,

an iso co r i a,

midriasis

ceguera o

miosis

(Houston, 1985; Lewis et al., 1994).

# Acetato de Megestrol #

Retinitis

hemorrágica,

Desprendimiento de retina (Bedford & Cotchin, 1983; Kunkle, 1984; Spiess et al., 1991)

Muchas Gracias!!!!

Pablo Sande, MV, PhD, DCLOVE p_sande@yahoo.com www.veteoftalmo.com.ar